Comorbid substance use disorders occur frequently in schizophrenia with significant detrimental effects to clinical outcome. Unfortunately, attempts to identify factors associated with comorbid substance use disorders (beyond demographic characteristics such as gender) have not been successful. This study examined an affect regulation model of comorbid substance use in schizophrenia with a focus on personality traits and coping. It was hypothesized that maladaptive coping and the traits of negative affect (NA) and disinhibition (DIS), but not trait positive affect (PA), would be associated with greater substance use problems. Thirty-nine patients with schizophrenia or schizoaffective disorder completed measures of personality traits, coping, and negative consequences associated with substance use. Traits were differentially associated with coping in that NA and DIS, but not PA, were associated with maladaptive coping including the use of drugs and alcohol to cope with stress. Alternatively, PA, but not DIS or NA, was related to adaptive coping strategies. Individuals high in NA and endorsing the use of drugs and alcohol to cope reported the greatest number of negative consequences from substance use. This finding held after controlling for gender. These results are consistent with an affect regulation model of substance use and suggest the advantage of examining the role of affect, traits, and coping in understanding comorbid substance use in schizophrenia.