Purpose: We sought to determine whether propranolol has adverse effects on cognitive function, depressive symptoms, and sexual function in patients treated for diastolic hypertension. subjects and methods: We performed a placebo-controlled trial among 312 men and women, 22 to 59 years of age, who had untreated diastolic hypertension (90 to 104 mm Hg). Patients were randomly assigned to treatment with propranolol (80 to 400 mg/day) or matching placebo tablets. Thirteen tests of cognitive function were assessed at baseline, 3 months, and 12 months. Five tests measured reaction time to, or accuracy in, interpreting visual stimuli; one test measured the ability to acquire, reproduce, and change a set of arbitrary stimulus-response sets; and seven tests measured memory or learning verbal information. Depressive symptoms and sexual function were assessed by questionnaires at baseline and 12 months. results: There were no significant differences by treatment assignment for 11 of the 13 tests of cognitive function at either 3 or 12 months of follow-up. Compared with placebo, participants treated with propranolol had slightly fewer correct responses at 3 months (33 ± 3 [mean ± SD] versus 34 ± 2, P = 0.02) and slightly more errors of commission at 3 months (4 ± 5 versus 3 ± 3, P = 0.04) and at 12 months (4 ± 4 versus 3 ± 3, P = 0.05). At 12 months, depressive symptoms and sexual function and desire did not differ by treatment assignment. Conclusions: Treatment of hypertension with propranolol had limited adverse effects on tests of cognitive function that were of questionable clinical relevance, and there were no documented adverse effects on depressive symptoms or sexual function. Selection of beta-blockers for treatment of hypertension should be based on other factors.