Nicotine addiction is a leading preventable disease and cause of death in the United States. Addressing the critical components that propagate the process of addiction could serve to bring about novel and innovative forms of treatment. Of particular interest is the role of the insula in modulating smoking addiction. A seminal study revealed that stroke patients with damage to the insula were able to quit smoking with ease and without urge. This disruption in smoking allowed them to remain abstinent to a greater extent than those with non-insula damage. The purpose of this prospective supplementary study was to further investigate the role of the insula alone and in combination with basal ganglia damage in nicotine withdrawal and smoking pleasure. Using 44 nonsmokers (who were smokers at the time of lesion onset) identified at the first month follow-up we examined somatic and affective symptoms of withdrawal, cravings, and other related smoking behaviors that could influence relapse on three additional follow-up sessions. Results found that patients with selective damage to the basal ganglia and combined damaged to the insula and basal ganglia had the lowest nicotine dependence and were able to overcome their smoking urges. In turn, these subjects were more likely to remain abstinent at 12 months, when examining all groups together. Additionally, as expected there were strong positive correlations between negative affect items, relief items, and level of difficulty in quitting at first month and smoking status at 12 months. Future research should consider how damage to these neural structures influences smoking behavior, such as predicting long-term drug cessation. Doing so could establish more effective treatment approaches and ultimately assist smokers who want to avoid relapse."