The five phases of the Prevent Injury and Enhance Performance (PEP) program were devised by the Santa Monica Sports Medicine Research Foundation [17]. These include dynamic warm-up, strengthening, plyometrics, agility training, and lower extremity stretching, with all exercises designed to be completed in 15–20 min. The results of the PEP program were first reported by Mandelbaum et al. [17] in a prospective nonrandomized study. A total of 1,885 female soccer players aged 14–18 participated in the program over two seasons. A 88 % decrease and 74 % decrease in ACL injuries was observed in the first and second seasons, respectively, in the intervention group. In 2008, Gilchrist et al. [5] reported the results of the PEP program in a randomized controlled trial involving female collegiate soccer players. The study included 583 athletes in the PEP intervention group compared to 852 in the control group and found a 3.3 times higher rate of noncontact ACL injury in the control group.

In 2004, Irmischer et al. presented the results of a plyometric-based knee ligament injury prevention (KLIP) program. Thirty-two women were randomized into the control group or intervention group. The intervention group participated in 9 weeks (18 sessions) of the KLIP program, which involved proper landing techniques for jump-landing-jump tasks. The results of the study demonstrate that the KLIP program was able to reduce the ground reaction forces (which included peak impact forces and rate of force development at landing) during a step-land protocol. The authors concluded that reducing these peak forces during landing could reduce the risk of ACL injury.

The clinical effects of the KLIPP program, however, are still unproven. In 2006, a prospective two-year study was conducted by [41] to determine if the KLIPP program would reduce the risk of ACL injury. A total of 1,439 high school female athletes (playing soccer, basketball, and volleyball) were recruited from 15 schools (112 teams) for two consecutive seasons. A total of 862 students participated in the control group and 577 in the treatment group. The incidence of noncontact ACL injuries 0.167 in the treatment group and 0.078 in the control group yielded an odds ratio of 2.05, which was not statistically significant (p > 0.05).

The Oslo Sports Trauma Research Center studied the effect of “The 11” program, a 15-min warm-up program for core stability, lower extremity strengthening, neuromuscular training, and agility. This was studied in a cluster randomized controlled study which included 1,091 female soccer players in the intervention group compared to 1,001 female soccer players in the control group [35]. A total of 396 (20 %) players sustained injuries. The authors noted no effect of the injury prevention program to decrease the injury rate; however, they noted that a significant portion of the intervention included soccer teams who did not complete most of the training sessions. In order to increase compliance with the program, the Oslo researchers and FIFA collaborated to create the “FIFA 11+” program to improve both the preventive effect of the previous “11” program as well as the compliance of players and coaches. The revised program (“The 11+”) provided variation and progression in its exercise selection, as well as a new set of structured running exercises suited better for a comprehensive warm-up program for training and matches. Soligard et al. [33, 34] reported using a cluster randomized trial that the players undergoing the “FIFA 11+” program had a significantly lower risk of overall injury, overuse injuries, and severe injuries compared to controls. In a recent randomized control trial [31], the FIFA 11+ has also been proven effective in reducing injuries among male collegiate soccer players. The injury rate was reduced by 46.1 %, and the time loss to injury decreased by 28.6 % in the competitive male collegiate soccer player. This was the first study to show success of a prevention program for male athletes.

Since 1990, 14 large-scale clinical trials with a variety of prevention programs (including those above) have been performed to determine the efficacy of ACL prevention programs. From these trials, several overarching strategies can be gleaned from their results. Evidence from these trials demonstrates that neuromuscular training programs are more effective in younger individuals. In a recent meta-analysis, Myer et al. [20] compared the risk of female athletes undergoing neuromuscular training ages 14–18 and 19–20 to those aged 20 years and above as reference. The 14–18- and 19–20-year-old female athletes demonstrated a reduced risk of sustaining ACL injuries by 72 % and 52 %, respectively.

Increased compliance to any ACL prevention program is critical to the success of a prevention program. In a meta-analysis, Sugimoto et al. [37] demonstrated that with a compliance rate of greater than 66 %, an ACL injury reduction rate of 82 % was observed. However, when the compliance rate decreased to less than 66 % or 33 %, the rates of ACL injury reduction were found to be 44 % and 12 %, respectively. As one would expect, the success of any ACL program depends on participant adherence. The same analysis demonstrated an inverse dose response associated between program training volume and ACL injury: the more time athletes spent in their respective training programs, the fewer ACL injuries they sustained.

Finally, programs that consist of multiple different types of exercises demonstrated increased effectiveness. In a separate meta-analysis, Sugoimoto et al. [36] demonstrated that training programs with multiple types of exercises had greater reduction in incidence of ACL injury compared to those with only a single exercise modality. Given the multifactorial nature of ACL injuries, it makes sense that a successful ACL prevention program would incorporate a variety of exercises within neuromuscular training.

Financially, ACL prevention programs have been shown to be cost-effective, at least in theory. In 2014, [38] created a decision-analytic model that was created to compare the cost-effectiveness of either an ACL prevention program versus a screening program. They enrolled hypothetical cohort of young athletes into three groups: (1) no training/screening, (2) ACL prevention program, (3) screening for high-risk athletes and enrolling only high-risk athletes in ACL prevention program. They concluded that the universal implementation of an ACL prevention training program could save $100 per player per season and reduce the incidence of ACL injury from 3 % to 1.1 % per season.