Background: Bipolar radiofrequency (RF) clamps have been shown to be capable of reproducibly creating transmural lesions with a single ablation in animal models. Unfortunately in clinical experience the bipolar clamps have not been as effective and often require multiple ablations to create conduction block. This study created a new experimental model using fresh, cardioplegically arrested human hearts turned down for transplant to evaluate the performance of a nonirrigated bipolar RF clamp. Methods: Nine human hearts turned down for transplant were harvested, and the Cox-Maze IV lesion set was performed with a nonirrigated bipolar RF clamp. In the first 7 hearts a single ablation was performed for each lesion. In the last 2 hearts a set of 2 successive ablations without unclamping were performed. The heart tissue was stained with 2,3,5-triphenyl-tetrazolium chloride. Each ablation lesion was cross-sectioned to assess lesion depth and transmurality. Results: A single ablation with the bipolar RF clamp resulted in 89% (469/529) of the histologic sections and 65% (42/65) of the lesions being transmural. Of the nontransmural sections, 92% occurred in areas with epicardial fat. Performing 2 successive ablations without unclamping resulted in 100% of the cross-sections (201/201) and lesions (25/25) being transmural. Conclusions: A single ablation failed to create a transmural lesion 35% of the time, and this was associated with the presence of epicardial fat. Two successive ablations without unclamping resulted in 100% lesion transmurality using the bipolar RF clamp.