Background: Left atrial appendage closure (LAAC) combined with radiofrequency catheter ablation is an emerging one-stop hybrid procedure for non-valvular atrial fibrillation (AF). This study was performed to compare the efficacy and safety of the Watchman device vs. the LAmbre device for this combined procedure. Methods: Two hundred and thirty two patients with AF who underwent the combined procedure were enrolled and divided into two subgroups depending on the device choice: the Watchman-combined group (n = 118) and the LAmbre-combined group (n = 114). The periprocedural and follow-up adverse events in both groups were documented. Results: The mean CHA2DS2-VASc score and HAS-BLED score in the Watchman-combined group and LAmbre-combined group were 3.7 ± 1.5 vs. 3.8 ± 1.5 and 2.5 ± 1.1 vs. 2.3 ± 1.1, respectively (all P > 0.05). Successful LAAC was achieved in all patients. The rate of major periprocedural complications and AF recurrence at 6 months post-procedure were similar between the Watchman-combined group and LAmbre-combined group (0.8 vs. 0.9%, P = 1.00; 22.0 vs. 15.8%, P = 0.23). During 2.6 ±0 .7 vs.1.6 ± 1.6 years follow-up, the rate of major clinical adverse events, including stroke and major bleeding, were comparable between the Watchman-combined group and the LAmbre-combined group (2.6 vs. 1.1% per 100 patient-years, P = 0.33). The intraprocedural peri-device leakage (PDL) rate was similar between the Watchman-combined group and the LAmbre-combined group (5.1 vs. 6.1%, P = 0.73), but the PDL rate was significantly higher at 3-6 months transesophageal echocardiography (TEE) follow-up than the intraprocedural PDL rate in both groups (21.6 vs. 5.1%; 36.6 vs. 6.1%, respectively), with a more obvious increase in minimal PDL rate in the LAmbre-combined group than the Watchman-combined group (36.6 vs. 21.6%, P < 0.05). Conclusion: The Watchman and LAmbre devices were comparable in efficacy and safety for the combined procedure. The minimal PDL rate at short-term TEE follow-up was higher in the LAmbre-combined group than the Watchman-combined group.