Background: The Positive and Negative Affect Schedule (PANAS) is a widely used measure of affect. A comprehensive psychometric evaluation among substance users, however, has not been published. Objective: To examine the psychometric properties of the PANAS in a sample of outpatient treatment substance users. Methods: We used pooled data from four randomized clinical trials (N = 416; 34% female, 48% African American). Results: A confirmatory factor analysis indicated adequate support for a two-factor correlated model comprised of Positive Affect and Negative Affect with correlated item errors (Comparative Fit Index = 0.93, Root Mean Square Error of Approximation = 0.07, chi(2) = 478.93, df = 156). Cronbach's alpha indicated excellent internal consistency for both factors (0.90 and 0.91, respectively). The PANAS factors had good convergence and discriminability (Composite Reliability > 0.7; Maximum Shared Variance < Average Variance Extracted). A comparison from baseline to Week 1 indicated acceptable test-retest reliability (Positive Affect = 0.80, Negative Affect = 0.76). Concurrent and discriminant validity were demonstrated with correlations with the Brief Symptom Inventory and Addiction Severity Index. The PANAS scores were also significantly correlated with treatment outcomes (e.g. Positive Affect was associated with the maximum days of consecutive abstinence from primary substance of abuse, r = 0.16, p = 0.001). Conclusion: Our data suggest that the psychometric properties of the PANAS are retained in substance using populations. Although several studies have focused on the role of Negative Affect, our findings suggest that Positive Affect may also be an important factor in substance use treatment outcomes.