Among chronic smokers, individual differences in subjective reactions to smoking may characterize important facets of nicotine dependence that relate to abstinence-induced craving, withdrawal symptom profiles, and risk for relapse. Although the negative reinforcing properties of smoking have achieved prominent positions in models of relapse (Baker, Brandon, & Chassin, 2004), vulnerability to relapse risk may also arise from seeking positive reinforcement from smoking (Shiffman & Kirchner, 2009). In this study, 183 cessation-motivated smokers provided subjective craving, positive and negative reactions to standardized cigarettes following overnight abstinence. Level of craving, negative mood, and positive mood after overnight abstinence were significantly predictive of withdrawal on quit-day. Increased positive reactions to smoking were uniquely predictive of relapse after quitting (Hazard Ratio = 1.22, p < .001). Individual differences in positive reactions to smoking may be important markers of neurobiological systems that promote dependence and interfere with cessation efforts.