Background: Percutaneous left atrial appendage closure (LAAC) reduces the incidence of stroke/bleeding events in patients with non-valvular atrial fibrillation, high risk of stroke, and contraindication in continuing anticoagulation therapy. Of them, patients with heart failure may remain at high risk of these events after LAAC. Method: Patients who underwent LAAC and were listed for the multi-center, prospectively collected OCEAN-LAAC registry, were eligible. Of them, individuals without baseline plasma B-type natriuretic peptide (BNP) levels and those dependent on hemodialysis were excluded. The prognostic impact of baseline plasma BNP levels on the incidence of death or stroke/bleeding events after LAAC was evaluated. Results: A total of 937 patients (median 78 years, 596 men) were included. The LAAC device was successfully implanted in 934 (98%) patients. Over the 366 (251, 436) days after the LAAC, 148 patients encountered a primary outcome. The common logarithm of baseline plasma BNP was independently associated with the primary outcome with an adjusted hazard ratio of 1.46 (95% confidence interval 1.06–2.18, p = 0.043). A calculated cutoff of 2.12 (equivalent to 133 pg/mL of plasma BNP level) significantly stratified the cumulative incidence of the primary outcome (29% vs. 21% for 2 years, p = 0.004). Conclusions: Using prospectively collected large-scale multi-center Japanese registry data, we demonstrated that a baseline higher plasma BNP level was independently associated with a higher incidence of stroke/bleeding events and mortality after LAAC. Further studies are warranted to understand the optimal therapeutic strategy for LAAC candidates with elevated baseline plasma BNP levels.