Percutaneous left-atrial appendage closure (LAAC) is an established method for preventing strokes in patients with atrial fibrillation, offering an alternative to oral anticoagulation. Various occluder devices have been developed to cater to individual anatomical needs and ensure a safe and effective procedure. In this retrospective, monocentric cohort study, we compare different LAAO devices with respect to clinical outcomes, LAA sealing properties, and device-related complications. We conducted a retrospective analysis of 270 patients who underwent percutaneous LAA closure in our center between 2009 and 2023. Patient data were extracted from medical records, including gender, age at implantation, indication, device type and size, laboratory values, LAA anatomy, periprocedural complications, ECG parameters, transthoracic and transesophageal echocardiography parameters (TTE and TEE), as well as medication at discharge. Moreover, fluoroscopy time and implantation duration, as well as post-implantation clinical events up to 1 year, were collected. Endpoints were bleeding events, recurrent stroke, thrombi on devices, and death. The implanted devices were the Watchman 2.5, Watchman FLX, Amplatzer Cardiac Plug (ACP), and Amulet. The procedural success rate was 95.7% (n = 265), with cactus anatomy posing the most challenges across all devices. The mean patient age was 75.5 ± 7.7 years, with 64.5% being male. The median CHA2DS2-VASc score was 4.8 ± 1.5 and the median HAS-BLED score was 3.8 ± 1.0. Indications for LAA closure included past bleeding events and elevated bleeding risk. Periprocedural complications were most commonly bleeding at the puncture site, particularly after ACP implantation (p = 0.014). Significant peridevice leaks (PDL) were observed in 21.4% of simple sealing mechanism devices versus 0% in double sealing mechanism devices (p = 0.004). Thrombi were detected on devices in six patients, with no subsequent ischemic stroke or thromboembolic event. Comparative analysis revealed no significant differences in the occurrence of stroke, transient ischemic attack (TIA), thromboembolic events, device-related thrombi, or mortality among different device types. A 62.3% relative risk reduction in thromboembolic events and 38.6% in major bleedings could be observed over 568.2 patient years. In summary, our study highlights the efficacy and safety of LAA closure using various occluder devices despite anatomical challenges. Our long-term follow-up findings support LAA closure as a promising option for stroke prevention in selected patient cohorts. Further research is needed to refine patient selection criteria and optimize outcomes in LAA closure procedures.