Background: As a preventive procedure, minimizing periprocedural risk is crucially important during left atrial appendage closure (LAAC). Methods: We included consecutive patients receiving LAAC at nine centres and assessed the relationship between baseline characteristics and the acute procedural outcome. Major procedural complications were defined as all complications requiring immediate invasive intervention or causing irreversible damage. Logistic regression was performed and included age and left-ventricular function. Furthermore, the association between acute complications and long-term outcomes was evaluated. Results: A total of 405 consecutive patients with a median age of 75 years (37% female) were included. 47% had a history of stroke. Median CHA2DS2-VASc score was 4 (interquartile range, 3–5) and the median HAS-BLED score was 3 (2–4). Major procedural complications occurred in 7% of cases. Low haemoglobin (OR 0.8, 95% CI 0.65–0.99 per g/dL, p = 0.040) and end-stage kidney disease (OR 13.0, CI 2.5–68.5, p = 0.002) remained significant in multivariate analysis. Anaemia (haemoglobin < 12 and < 13 g/dL in female and male patients) increased the risk of complications 2.2-fold. Conclusions: The major complication rate was low in this high-risk patient population undergoing LAAC. End-stage kidney disease and low baseline haemoglobin were independently associated with a higher major complication rate.