Background Research consistently shows drinking-to-cope (DTC) motivation is uniquely associated with drinking-related problems. We furthered this line of research by examining whether DTC motivation is predictive of processes indicative of poor emotion regulation. Specifically, we tested whether nighttime levels of episode-specific DTC motivation, controlling for drinking level, were associated with intensified affective reactions to stress the following day (i.e., stress-reactivity). Design and Methods We used a micro-longitudinal design to test this hypothesis in two college student samples from demographically distinct institutions: a large, rural state university (N = 1421; 54% female) and an urban historically Black college/university (N = 452; 59% female). Results In both samples the within-person association between daily stress and negative affect on days following drinking episodes was stronger in the positive direction when previous night’s drinking was characterized by relatively higher levels of DTC motivation. We also found evidence among students at the state university that average levels of DTC motivation moderated the daily stress-negative affect association. Conclusions Findings are consistent with the notion that DTC motivation confers a unique vulnerability that affects processes associated with emotion regulation.