Background: Left atrial appendage closure (LAAC) is a mechanical alternative for stroke prevention in patients at risk who cannot tolerate oral anticoagulation (OAC). Hypothesis: Our hypothesis was that the reduction of anticoagulation following LAAC results in a decrease of bleeding events and a rise in serum hemoglobin in a high-risk collective of patients with atrial fibrillation (AF). Methods: Bleeding events, use of erythrocyte concentrates, anticoagulation, embolic events, and serum hemoglobin levels before and following LAAC were compared over more than 4 years. Results: Seventy-five patients (CHA2DS2-VASc score 4.4 +/- 1.7, HAS-BLED score 4.6 +/- 1.1) were analyzed. Before LAAC (observation period 1.8 +/- 1.8 years), 67 patients experienced 1.8 +/- 1.4 bleeding events (0.9 +/- 1.3 major) per year resulting in 0.7 +/- 1.3 transfusions per year. After LAAC (2.6 +/- 2.0 years), 26 patients (p < .0001 vs. before) had 0.6 +/- 2.1 bleeding events (p < .0001), 0.2 +/- 0.6 major bleedings (p < .0001) and received 0.6 +/- 1.9 transfusions per year (p = .671). Fourteen patients had stroke before and 3 after LAAC (p = .008). Serum hemoglobin increased from initially 9.9 +/- 3.0 to 11.9 +/- 2.3 g/dL until the end of follow-up (p = .0005). Adverse embolic events did not differ before and after LAAC in our collective. Conclusion: In this clinical relevant cohort of AF patients with high risk for stroke and intolerance to OAC, we show that LAAC was able to reduce the rate of stroke and bleeding events, which translated into a rising serum hemoglobin concentration.