This study tested the hypothesis that metoprolol reduces the restenosis rate after percutaneous transluminal coronary angioplasty (PTCA) in native coronary arteries as compared to placebo. Apart from prognostic clinical effects in the treatment of patients with coronary heart disease, several in vivo and ex vivo studies have demonstrated antiproliferative and antiatherogenic effects of beta-blockers. In the present study, 192 male patients were randomized in a double-blind fashion to metoprolol sustained-release treatment or placebo starting at least 1 day before angioplasty. Lesion diameters and restenosis rates were evaluated using automatic edge detection systems. The study endpoint was the angiographic restenosis rate 4 months after PTCA. Ninety-seven randomized patients had a control angiography a mean of 4.5 months after PTCA. Dropouts were evenly distributed between the metoprolol and placebo groups. Lumen loss in the target lesion was 0.36 mm in the metoprolol group and 0.32 mm in the placebo group. Restenosis rates averaged 57.5% in the metoprolol group and 44.2% in the placebo group using conventional restenosis criteria. Taking metoprolol serum levels above 50 mmol/l as an indication of definite compliance with the metoprolol treatment, the restenosis rate was 58.3%. In conclusion, 95 mg of sustained-release metoprolol failed to reduce the restenosis rate following angioplasty in native coronary arteries.