Background Little is known about the interaction between individual and environmental determinants of physical activity, although this may be important information for the development of effective interventions. The goal of this paper is to investigate whether perceived neighborhood safety modifies associations between individual cognitions and sports participation. Methods Cross-sectional data were obtained from residents (age 25-75) of 87 neighborhoods in the city of Eindhoven, who participated in the Dutch GLOBE study in 2004 (N = 2474). We used multilevel logistic regression to analyze the interactions between perceived neighborhood safety and individual cognitions (attitude, self-efficacy, social influence, and intention) on sports participation (yes/no). Results In its association with sports participation, perceived neighborhood safety interacted significantly with self-efficacy and attitude (p < 0.05). Among persons who perceived their neighborhood as safe, a positive attitude was strongly associated with sports participation (OR = 2.00, 95%CI = 1.48-2.71). In contrast, attitude was not associated with sports participation in persons who perceived their neighborhood as unsafe (OR = 0.65, 95%CI = 0.34-1.24). Further, self-efficacy was significantly stronger associated with sports participation in persons who perceived their neighborhood as unsafe (OR = 1.85, 95%CI = 1.31-2.60) than in those who perceived their neighborhood as safe (OR = 1.19, 95%CI = 1.05-1.36). Social influence and intention did not interact with perceived neighborhood safety. Conclusions Associations between individual cognitions and sports participation depend on neighborhood circumstances, such as perceived neighborhood safety. Interventions to promote sports participation in adults should take the interaction between environmental and individual characteristics into account. More research is needed to find out the causal pathways in individual-environment interactions.