Deficits in prospective memory (PM; i.e., enacting previously learned actions at the right occasion) and risky decision-making (i.e., making choices with a high chance of undesirable/dangerous outcomes) are both common among individuals with substance use disorders (SUD). Previous research has raised the possibility of a specific relationship between PM and risk-taking, and the present study aimed to systematically study if PM provides unique variance in the prediction of risky decision-making. Two samples were included: (1) a group of 45 individuals with SUD currently in treatment, and (2) a nonclinical group of 59 university students with high-risk drinking and/or substance use. Regression analyses indicated that time-based, but not event-based, PM predicted increased risky behavior (e.g., risky sexual practices and criminal behaviors) in both groups after controlling for demographic, psychiatric, and substance use variables, as well as other neuropsychological functions. The current findings contribute to the growing literature supporting the role of PM as a predictor of everyday functioning, and suggest that cognitive rehabilitation may be an important avenue of research as an adjunct to traditional substance use treatment, particularly in addressing the potential adverse effects of PM deficits in the implementation of treatment-related homework activities and risk management strategies.