Objectives: The aim of this study was to investigate the procedural efficacy and safety of the novel Watchman FLX (Boston Scientific, Marlborough, Massachusetts) device for left atrial appendage occlusion (LAAO) and to assess the feasibility of intracardiac echocardiography (ICE) to guide implantation. Background: The Watchman FLX device for transcatheter LAAO was introduced for a simplified implantation in a wider range of LAA anatomies. Methods: This single-center study included consecutive patients undergoing LAAO with the Watchman FLX between March 2019 and January 2020 (N = 91). Patients underwent cardiac computed tomography (CT) imaging for pre-procedural planning. Initial procedures were guided by transesophageal echocardiography (TEE; n = 8) and thereafter by ICE (n = 83) from the left atrium. TEE and cardiac CT imaging were performed at 8 weeks’ follow-up. Results: Technical success was achieved in 90 (99%) patients, with the first device implanted in 86 (96%) procedures. Procedural success was 93.4%. Peri-procedural complications occurred in 5 (5.5%), with pericardial effusion being the most common (2.2%). Only 3.3% had a peri-device leak on TEE follow-up. No device-related thrombosis occurred. The mean device compression rate at end of procedure was 18.3 ± 7.7%, compared with 12.2 ± 7.8% by TEE at 8 weeks’ follow-up (p < 0.001) and 5.8 ± 8.8% by cardiac CT imaging at follow-up (p < 0.001). Conclusions: The Watchman FLX device was suitable for closure of a wide range of LAA anatomies, including shallow appendages. The follow-up closure rate was higher than previously reported with other devices. ICE from the left atrium was used, with high procedural success and a low complication rate, comparable to previous studies on LAAO.