Background The purpose of the study was to determine the efficacy and safety of left atrial appendage (LAA) closure with a micropuncture pericardial access approach and the new LARIAT+ suture delivery device. Methods Seventy-two patients with atrial fibrillation were enrolled to undergo telescopic micropuncture pericardial access and percutaneous ligation of the LAA with the LARIAT+ device. LAA closure was confirmed with transesophageal echocardiography (TEE) and contrast fluoroscopy immediately, then with TEE at 30 days and 90 days post-LAA ligation. Patients were monitored for 12 months by an independent clinical research organization for adverse events, stroke, embolic events and death of any cause. Results 72 patients were screened for the LARIAT+ procedure. Fourteen patients were screened failures (7 patients due to unfavorable anatomy and 7 patients with LAA thrombus). Fifty-eight patients underwent successful LAA ligation. All 58 patients had complete acute closure of the LAA. At 1 month 52 of 54 patients (96.3%) had LAA closure, while at 3 months 48 of 52 patients (92.3%) had LAA closure. There were no leaks greater than 3 mm at both 1 and 3 months. There were no device or procedural related complications, and only 1 30 day adverse event involving late pericardial effusion. There were no strokes, embolic events or deaths after 12 months. Conclusions LAA closure with the micropuncture pericardial access approach and the LARIAT+ device can be performed effectively with acceptably low periprocedural adverse events.