Retrograde cardioplegia (RC) delivery may result in suboptimal myocardial protection, due to leakage of cardioplegia to the right atrium. This study was undertaken to assess the efficacy of a double balloon cannula (DBC) occluding the coronary sinus ostium during RC. Fifteen patients were randomly assigned to receive RC via a conventional cannula or via the DBC. Cardioplegia was started at 200 ml/min, and the flow rate (Q) was adjusted to obtain a perfusion pressure (P) of 25-40 mmHg. Blood samples were collected at 13 different time points. The CPK-MB and TnI levels were measured on each sample. The use of the DBC was associated with increased P (P=0.03) at a lower Q (P=0.02). The CK-MB levels were significantly increased in both groups (P<0.0001). However, the use of the DBC was associated with lower levels of CK-MB (P=0.002). A similar trend was observed for the TnI levels (peak 5.1+/-1.8 ng/ml vs. 8.7+/-5 ng/ml, P=0.11). Occlusion of the coronary sinus ostium improved the hemodynamic efficiency of the RC, and this resulted in reduced perioperative ischemic myocardial damage.