Abstract Background Patients with atrial fibrillation (AF) are at risk for ischemic strokes, often originating from the left atrial appendage (LAA). Preventive LAA amputation (LAAA) during cardiac surgery has been shown to reduce ischemic stroke risk, both in patients with and without AF. However, the short-term safety and functional implication of LAAA in non-AF patients remain poorly understood. Besides possible surgical complications, there are suggestions that LAAA could lead to postoperative AF or influence neurohumoral changes resulting in fluid overload. Purpose To evaluate the safety of LAAA in patients without a history of AF undergoing routine cardiac surgery. Methods Patients underwent elective cardiac surgery between May 5 2015 and April 18 2018 in two high volume centers. Main inclusion criteria were a CHA2DS2-VASc≥ 2 and no history of AF. Patients without a history of AF, that participated in the PREDICT-AF study underwent concomitant LAAA and were compared with patients undergoing cardiothoracic surgery who were approached for participation in PREDICT-AF, but declined and subsequently did not undergo LAAA. Informed consent for the retrospective use of data was obtained through an opt-out procedure in these patients. The primary outcome of this analysis was the number of patients with any serious adverse event within 30 days postoperatively. Secondary outcomes were AF within 30 days postoperatively, death, rethoracotomy, time on extra corporal circulation(ECC) and heart failure related symptoms assessed through congestion on x-chest and weight trends. Adverse events were independently adjudicated by a cardiothoracic surgeon using pre-specified definitions. Results 150 patients in PREDICT-AF underwent LAAA. 284 Eligible patients declined participation and formed the control group. Patients in the LAAA group were more frequently male (87.3% vs 72.5%; p=0.001), were taller (176.0cm ± 8.2 vs 172.6cm ± 9.9; p<0.001) and weighed more (86.1kg CI[80.0, 92.2] vs 81.6kg CI[71.9, 91.1]; p=0.001) compared to controls. There were no significant differences in occurrences of serious adverse events (8% vs 12%; p=0.265), deaths (1.3% vs 1.8%; p=1) or rethoracotomies (3.3% vs 1.8%; p=0.483) between the LAAA and control group. Also, there was no difference in the incidence of postoperative AF (57, 38% vs 90, 31.7%; p=0.225), ECC time (104.5 minutes CI[81.0, 129.0] vs 98.0 CI[80.0, 124.5] p=0.371) or the presence of chest x-ray congestion (26.0% vs 27.8%; p=0.771) between the groups (Figure 1A). The spline plot of perioperative weight change from baseline, reveals no notable differences between the two groups (Figure 1B). Conclusion LAAA during routine cardiothoracic surgery is not associated with more surgical complications, postoperative atrial fibrillation or heart failure related symptoms. Given the generally high AF risk in patients undergoing cardiothoracic surgery, a strategy to preemptively resect the LAA may be feasible and safe.Figure 1 A & B