Summary Background Raised blood pressure is common after acute stroke and is associated with an adverse prognosis. We sought to assess the feasibility, safety, and effects of two regimens for lowering blood pressure in patients who have had a stroke. Methods Patients who had cerebral infarction or cerebral haemorrhage and were hypertensive (systolic blood pressure SBP >160 mm Hg) were randomly assigned by secure internet central randomisation to receive oral labetalol, lisinopril, or placebo if they were non-dysphagic, or intravenous labetalol, sublingual lisinopril, or placebo if they had dysphagia, within 36 h of symptom onset in this double-blind pilot trial. The doses were titrated up if target blood pressure was not reached. Analysis was by intention to treat. This trial is registered with the National Research Register, number N0484128008. Findings 179 patients (mean age 74 SD 11 years; SBP 181 SD 16 mm Hg; diastolic blood pressure DBP 95 SD 13 mm Hg; median National Institutes of Health stroke scale NIHSS score 9 IQR 5–16 points) were randomly assigned to receive labetolol (n=58), lisinopril (n=58), or placebo (n=63) between January, 2005, and December, 2007. The primary outcome—death or dependency at 2 weeks—occurred in 61% (69) of the active and 59% (35) of the placebo group (relative risk RR 1·03, 95% CI 0·80–1·33; p=0·82). There was no evidence of early neurological deterioration with active treatment (RR 1·22, 0·33–4·54; p=0·76) despite the significantly greater fall in SBP within the first 24 h in this group compared with placebo (21 17–25 mm Hg vs 11 5–17 mm Hg; p=0·004). No increase in serious adverse events was reported with active treatment (RR 0·91, 0·69–1·12; p=0·50) but 3-month mortality was halved (9·7% vs 20·3%, hazard ratio HR 0·40, 95% CI 0·2–1·0; p=0·05). Interpretation Labetalol and lisinopril are effective antihypertensive drugs in acute stroke that do not increase serious adverse events. Early lowering of blood pressure with lisinopril and labetalol after acute stroke seems to be a promising approach to reduce mortality and potential disability. However, in view of the small sample size, care must be taken when these results are interpreted and further evaluation in larger trials is needed. Funding UK National Health Service Research and Development Health Technology Assessment Programme.