Background The Prostate Cancer Prevention Trial (PCPT)a randomized placebo-controlled study of the efficacy of finasteride in preventing prostate canceroffered the opportunity to prospectively study effects of finasteride and other covariates on the health-related quality of life of participants in a multiyear trial. MethodsWe assessed three health-related quality-of-life domains (measured with the Health Survey Short Form36: Physical Functioning, Mental Health, and Vitality scales) via questionnaires completed by PCPT participants at enrollment (3 months before randomization), at 6 months after randomization, and annually for 7 years. Covariate data obtained at enrollment from patient-completed questionnaires were included in our model. Mixed-effects model analyses and a cross-sectional presentation at three time points began at 6 months after randomization. All statistical tests were two-sided. ResultsFor the physical function outcome (n = 16 077), neither the finasteride main effect nor the finasteride interaction with time were statistically significant. The effects of finasteride on physical function were minor and accounted for less than a 1-point difference over time in Physical Functioning scores (mixed-effect estimate = 0.07, 95% confidence interval [CI] =-0.28 to 0.42, P =. 71). Comorbidities such as congestive heart failure (estimate =-5.64, 95% CI =-7.96 to-3.32, P <. 001), leg pain (estimate =-2.57, 95% CI =-3.04 to-2.10, P <. 001), and diabetes (estimate =-1.31, 95% CI =-2.04 to-0.57, P <. 001) had statistically significant negative effects on physical function, as did current smoking (estimate =-2.34, 95% CI =-2.97 to-1.71, P <. 001) and time on study (estimate =-1.20, 95% CI =-1.36 to-1.03, P <. 001). Finasteride did not have a statistically significant effect on the other two dependent variables, mental health and vitality, either in the mixed-effects analyses or in the cross-sectional analysis at any of the three time points. ConclusionFinasteride did not negatively affect SF36 Physical Functioning, Mental Health, or Vitality scores. © 2012 The Author.