Previous research has found that the location, type and mechanisms of injuries in lacrosse players vary by gender. The patterns and risk factors of injuries in lacrosse players are still not well known. The study population consists of lacrosse players who utilised the accident medical insurance provided to US Lacrosse members. Cluster analysis was used to explore the aetiology of lacrosse-related injuries. Between 2002 and 2006 there were 593 game injuries, 496 in men and 97 in women. There were six clusters of injuries in women and five clusters of injuries in men. Play scenarios resulting in injury differed by the position played. In all the five injury clusters in males, the primary injury mechanism was by contact, either with another player, a stick or a ball. In women, body-to-body and stick-to-body, and no contact were the most common injury mechanisms. In both genders, the majority of injuries occurred during legal play. These results provide a picture of high-risk situations that lead to injuries in male and female lacrosse players. Future efforts should be made to confirm these results through epidemiologic studies. Further research should also address the effectiveness of interventions that could reduce the risk of injury in these situations.