Background: Prominent theories of drug use underscore the importance of considering the inter-relationships (e.g., reciprocal relations, indirect effects) of determinants of drug use behavior. In the area of smoking, few studies have examined multiple determinants of cessation in this way, and in prospective analyses. The current study is an examination of the prospective cross-lagged relationships among five intrapersonal determinants of cessation. Methods: Data from a longitudinal cohort study on racial differences in the process of smoking cessation were used to examine reciprocal relations among abstinence motivation, abstinence self-efficacy, positive affect, negative affect, and craving. Each of these five measures assessed on the quit day were regressed onto the same measures assessed 1–2 weeks pre-quit. The relationships of these variables at quit day with 1-week post-quit abstinence from smoking were also examined. Results: When the five variables were examined simultaneously in a cross-lagged path analysis, motivation and self-efficacy, and self-efficacy and positive affect showed cross-lagged relations. Only self-efficacy on the quit day uniquely predicted 1-week post quit abstinence. There were significant indirect effects of motivation and positive affect on cessation via self-efficacy. Conclusions: The current study reaffirms the importance of motivation and self-efficacy in smoking cessation, and suggests that positive affect may play a role in smoking cessation.