Objectives: To evaluate the performance of the US Centers for Disease Control's health-related quality of life (HRQOL) scale among 522 college students. Methods: Chi-square analysis assessed scale construct validity and analysis of variance (ANOVA) with selected tobacco, alcohol, and substance use variables assessed known-groups validity of the scale's Healthy Days index. Results: Patterns of association among scale items were consistent with those hypothesized. ANOVA analyses revealed significant (P less than 0.05) associations between the Healthy Days index and selected variables in predicted directions. Conclusions: Preliminary evidence is provided that the HRQOL scale could serve as part of program evaluation, intervention, and surveillance efforts among college students.