The aim of the present study was twofold: to assess the safety of ablating the atrial free wall using RF current; and to assess the effect of a single dose of intravenous heparin followed by aspirin once daily to prevent thrombus formation after RF ablation. Temperature and power guided catheter ablation were evaluated. Twenty pigs were randomized to power or temperature guided unipolar RF catheter ablation. Ten animals received a bolus of heparin (150 U/kg) followed by 150-mg aspirin daily, and ten served as controls. A mid-sternal thoracotomy was performed 5-7 days later. The ability of a lesion to resist an increased transmural atrial pressure was examined by inflating a cuff around the pulmonal artery. Transmural lesions were found in all animals. Right atrial pressure was increased from 5 to 30 mmHg with no sign of perforation. In 11 of 20 (55%) animals, 1-3 lesions were found in the lungs (diameter 4-18 mm). The localization of these lesions corresponded to the lesions in the atria. There were no differences in the energy delivery modes with regard to the number of animals with lung lesions. Lesions with thrombus formation were found in four animals in the heparin/aspirin group and in nine animals in the control group. The incidence of thrombi was significantly smaller in the treatment group. There were no differences between temperature and power guided catheter ablation with regard to the size of the atrial lesions or to the incidence of thrombus formation. Transmural lesions induced in the right atrium by RF energy are resistant to increases in transmural pressure. However, lung tissue overlying the ablated target may be injured by the RF energy delivered. The combination of a single dose intravenous heparin followed by aspirin daily may reduce the incidence of thrombus formation.