The effect of dihydropyridines in patients with unstable angina is discouraging. To find out the effect of the non-dihydropyridine-like calcium-channel blocker diltiazem, a randomised, double-blind trial was conducted comparing diltiazem with glyceryl trinitrate, both given intravenously, in 129 patients with unstable angina. The endpoints were refractory angina or myocardial infarction, individually and as a composite endpoint. Refractory angina alone or together with myocardial infarction occurred significantly less commonly in the diltiazem group. While patients were on the trial drugs the numbers with refractory angina were 6 (10%) in the diltiazem group versus 17 (28%) in the glyceryl trinitrate group (relative risk 0.36, p = 0.02), and the numbers with refractory angina and myocardial infarction were 9 (15%) versus 23 (38%) (relative risk 0.40, p = 0.007). Over 48 h the number were: refractory angina 8 (13%) versus 18 (30%), relative risk 0.45, p = 0.03, and refractory angina and myocardial infarction 12 (20.0%) versus 25 (41%), relative risk 0.49, p = 0.02. Patients in the diltiazem group had better (p < 0.05) event-free survival while taking the drugs. Heart-rate pressure product was reduced significantly only by diltiazem (p < 0.05). The incidence of bradyarrhythmias did not differ significantly. Atrioventricular conduction disturbances occurred in 5 (8%) patients in the diltiazem group but were not seen in the glyceryl trinitrate group (p = 0.03). These disturbances could be reversed by decreasing the dose of the drug or withdrawing it. No temporary pacemakers were required. Headache requiring an analgesic or dose adjustment occurred significantly less in the diltiazem group: 3 (5%) versus 15 (25%), relative risk 0.20 (p < 0.004). These results indicate that intravenous diltiazem, compared with intravenous glyceryl trinitrate, significantly reduces ischaemic events and can be used safely in patients with unstable angina.