Decision making is thought to play a key role in psychostimulant relapse, but very few studies have addressed the issue of how to counteract decision-making deficits in addicted individuals. According to the somatic marker framework, pervasive decision-making problems in addicted individuals may relate to abnormalities in the processing of emotional signals that work to anticipate the prospective outcomes of potential decisions. The present study was conducted to test whether the induction of different emotional states (positive, negative, or drug-related) could either normalize or further impair decision-making performance in male cocaine polysubstance-using individuals (CPSI), as indexed by the Iowa gambling task (IGT). Forty-two CPSI and 65 healthy control individuals (all males) were randomly allocated in four affective conditions using a parallel-group design. Participants in the different conditions performed the IGT during exposure to neutral, positive, negative, or drug-related sets of affective images. The results showed that the CPSI exposed to the negative affective context showed a preference for the risk-averse safe choices of the IGT and had a net performance indistinguishable from that of controls. On the other hand, CPSI exposed to positive, drug-related, and neutral contexts showed the typical pattern of disadvantageous performance in the IGT and performed significantly poorer than controls. The impact of the negative mood induction could not be explained in terms of baseline differences in decision-making skills, personality traits related to sensitivity to reward/punishment, or trait positive/negative affect. We conclude that negative mood induction can normalize decision-making performance in male CPSI, which may have important implications for the treatment of cocaine use-related disorders.