High-power, short-duration (HPSD) radiofrequency ablation (RFA) reduces procedure time; however, safety and efficacy thresholds vary with catheter design. The study sought to determine optimal HPSD ablation conditions with a novel flexible-tipped, contact force–sensing RFA catheter. RFA lesions were created in thigh muscle (16 swine) over a range of conditions (51–82 W, 2–40 g, 8–40 mL/min irrigation). An intracardiac study was performed (12 swine) to characterize steam pop thresholds. Lesions were created in a second intracardiac study (14 swine, n = 290 pulmonary vein isolation PVI lesions) with combinations of radiofrequency power, duration, and contact force. PVI was tested, animals were sacrificed, and lesions were measured. The likelihood of coagulation formation in the thigh model was <20% when power was ≤79 W, when contact force was ≤40 g, when duration was ≤11 seconds, and when irrigation rates were 8 to 40 mL/min. The impact of contact force on lesion safety and efficacy was more pronounced using HPSD (60 W/8 seconds) compared with conventional ablation (30 W/45 seconds) (P = .038). During PVI, focal atrial lesions ranged in width from 4.2 to 12.5 mm and were transmural 80.8% of the time. PVI was achieved in 13 of 14 veins. Logistic regression identified that the optimal parameters for radiofrequency application were 60 to 70 W with a duration <8 seconds and <15 g contact force. Optimal HPSD lesions with this this flexible-tipped, force-sensing RFA catheter were created at 60 to 70 W for <8 seconds with <15 g contact force. Chronic studies are ongoing to assess radiofrequency parameter refinements and long-term lesion durability using these conditions. Display omitted