Objective To assess the role of dutasteride in preventing clinical progression of benign prostatic hyperplasia in asymptomatic men with larger prostates. Design Post hoc analysis of four year, double blind Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study Participants 1617 men randomised to dutasteride or placebo with a prostate size >40 mL and baseline International Prostate Symptom Score (IPSS) <8. Subjects who took medications for benign prostatic hyperplasia were excluded at study entry. Interventions Placebo or dutasteride 0.5 mg daily. Main outcome measures Comparison of risk of clinical progression of benign prostatic hyperplasia at four years (defined as a ≥4 point worsening on IPSS, acute urinary retention, urinary tract infection, or surgery related to benign prostatic hyperplasia). Results 825 participants took placebo, 792 took dutasteride. A total of 464 (29%) experienced clinical progression benign prostatic hyperplasia, 297(36%) taking placebo, 167 (21%) taking dutasteride (P<0.001). The relative risk reduction was 41% and the absolute risk reduction 15%, with a number needed to treat (NNT) of 7. Among men who had acute urinary retention and surgery related to benign prostatic hyperplasia, the absolute risk reduction for dutasteride was 6.0% and 3.8%, respectively. On multivariable regression analysis adjusting for covariates, dutasteride significantly reduced clinical progression of benign prostatic hyperplasia with an odds ratio of 0.47 (95% CI 0.37 to 0.59, P<0.001). Analysis of time to first event yielded a hazard ratio of 0.673 (P<0.001) for those taking dutasteride. Sexual adverse events were most common and similar to prior reports. Limitations Further prospective studies may be warranted to demonstrate generalisability of these results. Conclusions This study is the first to explore the benefit of treating asymptomatic or mildly symptomatic men with an enlarged prostate. Dutasteride significantly decreased the incidence of benign prostatic hyperplasia clinical progression.