Problems with memory and attention are common to both schizophrenia and alcohol dependence. The objectives of this study were to examine the effect of acamprosate treatment on cognition and to assess whether the changes in drinking patterns or psychotic symptoms were related to changes in cognitive functioning. Outpatients with schizophrenia spectrum disorders and alcohol dependence (n = 23) were randomized (double-blind) to either acamprosate or placebo treatment for 12 weeks. Assessments (baseline and week 12) included alcohol use, symptoms of psychosis, memory, and attention. The results showed that acamprosate had no effect on cognitive functioning and that there was no relationship between change in alcohol consumption or psychotic symptoms and change in cognitive functioning in this sample of patients. The finding that acamprosate had no negative effects on cognition is clinically relevant and reinforces previous reports that acamprosate can be used safely for alcohol reduction in this group of patients.