Background: Transcatheter left atrial appendage closure (LAAC) is performed in patients unsuitable for long-term anticoagulation, predominantly due to prior bleeding events. The study aimed to investigate the incidence and predictors of clinically significant bleeding (CSB) post-LAAC. Methods: Consecutive patients after LAAC with an Amplatzer or WATCHMAN device were analyzed (05.2014–11.2019). Bleeding was classified as CSB when associated with at least one of the following: death, ≥2 g/dL hemoglobin drop, ≥2 blood units transfusion, critical anatomic site, or hospitalization/invasive procedure. Results: Among 195 patients (age 74 (68–80), 43.1% females, HAS-BLED score 2.0 (2.0–3.0)), during median follow-up of 370 (IQR, 358–392) days, there were 15 nonprocedural CSBs in 14 (7.2%) patients. Of those, 9 (60.0%) occurred during postprocedural dual antiplatelet therapy (DAPT) (median 46 (IQR: 16–60) days post-LAAC) vs. 6 (40%) after DAPT discontinuation (median 124 (81–210) days post-LAAC), translating into annualized CSB rates of 14.0% (per patient-year on DAPT) vs. 4.6% (per patient-year without DAPT). In 92.9% (13/14) of patients, the post-LAAC nonprocedural CSB was a recurrence from the same site as bleeding pre-LAAC. In the multivariable model, admission systolic blood pressure (SBP) > 127 mmHg (HR = 10.73, 1.37–84.26, p = 0.024), epistaxis history (HR = 5.84, 1.32–25.89, p = 0.020), permanent atrial fibrillation (AF) (HR = 4.55, 1.20–17.20, p = 0.025), and prior gastrointestinal bleeding (HR = 3.35, 1.01–11.08, p = 0.048) predicted post-LAAC CSB. Conclusions: Nonprocedural CSBs after LAAC, with a similar origin as the pre-LAAC bleedings, were observed predominantly during postprocedural DAPT and predicted by elevated admission SBP, prior epistaxis, permanent AF, and gastrointestinal bleeding history. Whether a more reserved post-LAAC antiplatelet regimen and stringent blood pressure control may improve LAAC outcomes remains to be studied.