OBJECTIVE: To compare quality of life in elderly patients with isolated systolic hypertension allocated randomly to groups to receive placebo or active treatment in the Systolic Hypertension in the Elderly Trial. DESIGN: Double-blind randomized controlled trial. METHODS: Patients aged 60 years were allocated randomly to groups to receive first-line treatment with nitrendipine (with second- and third-line enalapril and hydrochlorothiazide) or placebo. Trained interviewers administered trail-making tests (Trail A and B), Brief Assessment Index (a measure of depressed mood) and four subscales from the Sickness Impact Profile (Ambulation, Social Interaction, Sleep and Rest, and Home work). RESULTS: Six hundred and ten patients completed a baseline and at least one follow-up questionnaire. Trail-making scores were slower in actively treated patients, especially in the first 6 months of follow-up when the between-group effect sizes were 0.25 [95% confidence interval (CI) 0.07 to 0.43] for Trail-making A and 0.13 (95% CI -0.05 to 0.31) for Trail-making B. Across the 4 years of follow-up, patients receiving active treatment were more likely to report problems on the Social Interaction scale than were placebo-treated patients (odds ratio 1.32, 95% CI 1.02 to 1.69), equivalent to a 7% difference. There were no significant differences between active and placebo treatment in the other Sickness Impact Profile dimensions or in the measure of depression. CONCLUSIONS: Active treatment in the Systolic Hypertension in Europe trial was associated with some small adverse impacts on quality of life.