BACKGROUND Phrenic nerve (PN) injury is a potential complication that can occur during superior vena cava (SVC) isolation to cure atrial fibrillation (AF). Avoiding radiofrequency (RF) energy delivery is the safer alternative but may result in failed isolation. High-output PN pacing above the ablation site (upstream PN pacing) to confirm whether the PN is intact is a promising technique to avoid PN injury. This study was conducted to elucidate the safety of delivering RF energy at the site of capture of the right PN using upstream high-output pacing during electrical SVC isolation. METHODS SVC isolation was conducted in 41 drug-resistant AF patients. When high-output pacing (25 mA) from the distal tip of the ablation catheter captured the PN at the right atrial-SVC junction, upstream PN pacing (cycle length: 1000-1500 ms) was applied during RF delivery. The application of RF energy was stopped upon the failure or weakness of diaphragmatic twitching. The feasibility of SVC isolation using upstream PN pacing was investigated. RESULTS In all 41 patients, SVC isolation was successfully achieved. RF energy was delivered at the PN capture site in 26 patients (154 ± 138 second, 18 ± 5 W), and upstream PN pacing was successfully applied in all of the patients. Out of 46 SVC isolations, including five repeated sessions, PN injury occurred in one patient, who recovered spontaneously within 2 weeks. CONCLUSIONS Upstream PN pacing may be effective for the safe completion of SVC isolation and to reduce the severity of PN injury.