AbstractAims: Radial artery spasm remains the major limitation of transradial approach for percutaneous coronary interventions. The aim of our study was to evaluate the efficacy of vasodilators in the prevention of radial artery spasm during percutaneous coronary interventions. Methods and results: 1,219 patients were consecutively randomized to receive placebo (n = 198), molsidomine 1 mg (n = 203), verapamil 2.5 mg (n = 409), 5 mg (n = 203) or verapamil 2.5 mg and molsidomine 1 mg (n = 206). All drugs were administered through the arterial sheath. The primary end point was the occurrence of a radial artery spasm defined by the operator as severe limitation of the catheter movement, with or without angiographic confirmation. Main characteristics including age, sex, wrist and arterial sheath diameters and procedure duration were identical across the groups. The rate of radial artery spasm was lowest in patients receiving verapamil and molsidomine (4.9%), compared to verapamil 2.5 mg or 5 mg (8.3 and 7.9%), or molsidomine 1 mg (13.3%); and placebo (22.2%) (P < 0.0001). Conclusion: Radial artery spasm during transradial percutaneous interventions was effectively prevented by the administration of vasodilators. The combination of verapamil 2.5 mg and molsidomine 1 mg provided the strongest relative risk reduction of spasm compared to placebo and should therefore be recommended during percutaneous coronary interventions through the radial approach. © 2006 Wiley‐Liss, Inc.