Although physical activity is often believed to be influenced by both environmental and individual factors, little is known about their interaction. This study explores interactions of perceived safety and social neighborhood factors with psychosocial cognitions for leisure-time walking. Cross-sectional data were obtained from residents (age 25-75 years) of 212 neighborhoods in the South-East of the Netherlands, who participated in the Dutch GLOBE study in 2004 (N = 4395, survey response 64.4%). Direct associations of, and interactions between perceived neighborhood safety, social neighborhood factors (social cohesion, social network and feeling at home) and psychosocial cognitions (attitude, self-efficacy, social influence and intention) on two outcomes of leisure-time walking [yes versus no (binary), and among walkers: minutes per week (continuous)] were analyzed in multilevel regression models. The association between attitude and participating in leisure-time walking was stronger in those who felt less at home in their neighborhood. Social influence and attitude were stronger associated with participation in leisure-time walking in those who sometimes felt unsafe in their neighborhood. A positive intention was associated with more minutes walked in those who perceived their neighborhood as unsafe among those who walked. Only limited support was found for interactions between neighborhood perceptions and psychosocial cognitions for leisure-time walking.