Retrograde delivery of cardioplegic solutions has recently been the subject of renewed interest, but the reliability of this technique has not been assessed in large clinical series. From 1980 to 1989, we used retrograde coronary sinus perfusion as the exclusive means of cardioplegia delivery in 500 consecutive patients undergoing aortic valve replacement, either isolated (359 patients) or combined with another valve or coronary procedure (141 patients), The coronary sinus was always cannulated under direct vision after bicaval cannulation with snaring. Cold crystalloid cardioplegia was delivered retaogradely at an average flow rate of 100 mL/min in conjunction with topical and systemic (25 °C hypothermia. The mean cross-clamp time was 83 ± 23 minutes (±the standard deviation). There were 31 hospital deaths (6.2%), 20 of which were cardiac related. Transient hemodynamic instability (defined as a need for inotropic agents for less than 24 hours postoperatively) occurred in 16 patients (3.2%), whereas a true low-output syndrome developed in 60 patients (12%). The incidence of clinically significant supraventricular arrhythmias and of permanent conduction defects was 7.4% and 1.2%, respectively. There were three nonfatal coronary venous injuries during our early experience. We conclude that coronary sinus perfusion is a safe and effective means of delivering cardioplegia in aortic valve operations. While providing a degree of myocardial protection similar to that reported with anterograde cardioplegia, the coronary sinus technique offers distinct advantages, in particular, the avoidance of perfusion-related coronary artery complications and the opportunity to repeat cardioplegia administration without interrupting the procedure. As another attractive feature of the coronary sinus route is to ensure homogeneous distribution of cardioplegia beyond coronary artery occlusions, the present study, by establishing its reliability on a large clinical scale, supports the more liberal use of this approach in select subsets of patients having coronary artery procedures. © 1990.