Background: Stimuli that are regularly associated with alcohol intake (AI) may acquire incentive salience, while other reinforcers can be devalued. We assessed whether brain activation elicited by (1) alcohol associated, (2) affectively positive, and (3) negative versus neutral stimuli is associated with the subsequent risk of relapse.Methods: Twelve detoxified alcoholic subjects (6 women and 6 men) and 12 age‐matched and gender‐matched healthy control subjects were assessed with functional magnetic resonance imaging (fMRI) and a fast single‐event paradigm using standardized affective and alcohol‐associated pictures. Patients were followed for 6 months and AI was recorded.Results: In alcoholic subjects, compared with healthy control subjects, (1) alcohol‐related versus neutral visual stimuli elicited increased activation in the prefrontal (PFC; BA 6 and 10) and cingulate cortex (BA 23 and 24), precuneus and adjacent parietal cortex; (2) positive versus neutral stimuli elicited increased activation in the anterior cingulate cortex (ACC; BA 24), PFC (BA 10), ventral striatum and thalamus; and (3) negative versus neutral stimuli elicited increased activation in the PFC (BA 10). Seven alcoholic subjects relapsed. Within the follow‐up period of 6 months, the number of subsequent drinking days (DD) and the amount of AI were inversely correlated with brain activation elicited by positive versus neutral stimuli in the thalamus (DD: r=−0.63, p=0.03; AI: r=−0.63, p=0.03) and in the ventral striatum (DD: r=−0.60, p=0.04; AI: r=−0.48, p=0.11).Conclusions: In this study, brain activation elicited by briefly presented alcohol‐associated stimuli was not associated with the prospective risk of relapse. Unexpectedly, alcoholic subjects displayed increased limbic brain activation during the presentation of affectively positive but not negative stimuli, which may reflect a protective factor in detoxified alcoholic subjects.