In an evaluation of the theoretical foundations of behavior change, the current study examined whether social cognitive (SCT) variables mediated treatment effects on physical activity and nutrition in the recently reported Guide-to-Health trial (GTH). Adults (N = 661) were assessed at baseline, seven months and 16 months to examine whether treatment-related changes in SCT variables at seven months mediated change in nutrition and physical activity at 16 months. GTH treatment effects were mediated by self-efficacy, self-regulation and social support; self-regulation mediated self-efficacy. Social-cognitive variables explained only part of the treatment effects suggesting future investigations evaluate the environmental-selection and affective processes of behavior change.