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Background: Minimally invasive cardiac surgery has increasingly been used for patients with valvular pathology. Two techniques of aortic occlusion are utilized with this technique: transthoracic aortic clamp (TTC) and endoaortic balloon occlusion (EAO). Both possibilities present peculiar advantages and limitations whose current evidence is based on few observational studies. We performed an analysis with the primary objective to evaluate outcomes and the incidence of major complications of these two techniques. Methods: The data of 258 patients who underwent minimally invasive mitral valve surgery through right mini-thoracotomy from January 2013 to July 2018 were reviewed. One hundred sixty-five patients were operated on with TTC and in 93 cases EAO was used. Univariate and multivariate analyses were performed to identify predictors of adverse outcome. Results: The mean age of the cohort was 60.4±13.9 years, patients with TTC were significantly older and had higher EuroSCORE II and reoperations were carried out mostly with EAO. Isolated mitral valve surgery was mostly performed (74%) and in 26% of the cases, other procedures were combined. No differences were detected in terms of types of operation, cardiopulmonary bypass (CPB) and cross-clamp times between the two techniques. Similar postoperative troponin I and CK-Mb values were recorded. Twenty-four patients (11%) suffered at least one complication. Of note, a new neurologic deficit occurred in six patients; in four cases a cerebral stroke, with all patients in the EAO group (P=0.06). There was no case of aortic dissection, no patient suffered peripheral ischemia nor femoral vessels complications. Thirty-day mortality was 1.9% (TTC 1.2% vs. EAO 3.2%; P=0.51), 30-day mortality excluding reoperations was 1.2% (TTC 1.2% vs. EAO 1.1%; P=0.61). Conclusions: Both techniques proved to be safe. Although non-statistically significant, there was a higher rate of cerebral stroke in the EAO group. However, EAO system shows technical advantages in avoiding tissue dissection and remains our choice in redo operations.