Background Most patients undergoing left atrial appendage closure (LAAC) are elderly individuals with atrial fibrillation (AF) and many comorbidities, which may elevate the risk for complications associated with contrast agents with fluoroscopic image-guided procedure. . Objectives This retrospective study of patients with AF at high risk for use of contrast agents evaluated the feasibility and safety of LAAC using Percutaneous and Non-fluoroscopic procedure with transesophageal echocardiography (TEE) as the only image guidance relative to those under fluoroscopic image guidance. Methods From September 2017 to December 2020, a cohort of 126 consecutive eligible patients with AF undergoing LAAC at our center were retrospectively recruited and divided into 2 groups according to image guidance modality, namely, a TEE group (n = 32; mean age, 75.4 ± 7.9 years; 25 (78.1%) with stage III chronic kidney disease [preoperative eGFR, 52.7 ± 8.8 mL/min/1.73m ²] and 7 (21.9%) allergic to contrast agent) and a fluoroscopic group (n = 94; mean age, 65.7 ± 10.0 years). Propensity score matching was used to adjust for baseline differences. Results Propensity-score matching yielded 25 pairs of patients with similarly distributed age (72.9 ± 6.9 vs. 73.1 ± 4.9 years, p = .925), gender (10:15 vs 11:14, p = 1), weight (68.3 ± 11.2 vs. 68.1 ± 12.3 kg, p = .948) and ALT level (20.0 ± 9.8 vs. 22.5 ± 14.2 U/L, p = .482). The LAA was successfully occluded in all patients with statistically similar success rate (100% vs. 100%, p = 1), hospitalization duration (5.0 [3.0, 7.0] vs. 5.0 [3.0, 6.0] days, p = .498), and rates of complications: 1 (4.2%) pericardial effusion and 1 (4.2%) residual shunt in the TEE group, and 5 (20%) residual shunts, 1 (4.2%) pericardial effusion, 1 (4.2%) myocardial infarction and 1 (4.2%) access-related complications in the fluoroscopic group. There were no deaths. The overall incidence rate of all procedure-related complications (6.2% vs . 18.1%, p = .153) at mean 22.2±4.5 months follow-up was statistically similar. Conclusion In patients with AF of high risk for use of contrast agents, LAAC under non-fluoroscopic guidance appears feasible and safe with similar outcomes to that under fluoroscopic guidance.