The goal of this study was to develop and test a new radio frequency thermal balloon system to allow longer balloon inflations at lower temperature levels than have been used with standard (laser) thermal balloon angioplasty. Radio frequency thermal capabilities were combined with perfusion balloon technology, creating a thermal-perfusion balloon catheter system for prolonged thermal inflations. Twenty-five dogs underwent thermal-perfusion angioplasty at 37 degrees, 60 degrees, or 80 degrees C for 1.5, 5, or 15 minutes with angiographic and morphologic assessments at 24 hours (n = 17) or 4-6 weeks later (n = 8). Treated segments and side branches remained patent. No coronary spasm, occlusive thrombus, or ischemic myocardial infarction occurred. Histologic extent of thermal injury in treated segments was proportional to treatment duration. Thus the thermal-perfusion balloon angioplasty system may be safely applied in canine coronary arteries. Integrating thermal and perfusion technologies provides prolonged treatment duration at moderate temperatures without excessive tissue damage.