Question: Are muscle strength, flexibility, body structure or static lower limb posture associated with increased risk of hamstring or quadriceps muscle strain injury in soccer or rugby league players? Design: prospective cohort study. Participants: Soccer (n=294) and rugby league (n=201) players ranging from amateur to professional performance. Outcome measures: Prior to commencement of the 2008 and 2009 playing seasons, players completed an injury history questionnaire and a battery of reliable physical assessments, including anthropometry, vertical jumps, anterior step up, incline single-leg squats, modified Thomas Test (MTT), active knee extension (AKE) for hamstring length, combined MTT/AKE and static postural photographs. Injury surveillance and exposure data were collected for the following playing season. Results: During surveillance there were 19 players with hamstring and 23 with quadriceps strains. Those with a sitting height (trunk length measured whilst sitting on a 40cm box, minus the 40cm) greater than 141.4cm (OR=1.481; p=0.033) and a history of hamstring injury in the previous 12 months (OR=2.497; p=0.019) were independent predictors of hamstring strain, in both soccer and rugby league. Knee hyperextension (OR=3.893; p=0.040) and sustaining a quadriceps injury in the previous 12 months (OR=6.836; p=0.012) were independent predictors of quadriceps strain, regardless of sport. Conclusion: In this multivariate analysis, muscle-specific previous injury and aspects of body structure were independent risk factors for sustaining hamstring and quadriceps injuries. These results provide a greater understanding of the factors influencing hamstring and quadriceps muscle strains and may contribute to future preventative or rehabilitative strategies.