Recent studies have suggested an increased risk of stroke in patients undergoing minimally invasive mitral-valve surgery with retrograde perfusion when compared with antegrade perfusion. The aim of the present study was therefore to evaluate the impact on early outcome of retrograde arterial perfusion (RAP) strategy vs antegrade arterial perfusion strategy in a consecutive large cohort of patients who underwent minimally invasive mitral-valve surgery through a right minithoracotomy. Between 2003 and 2012, 1280 consecutive patients underwent first-time minimally invasive mitral-valve surgery at our institution. A total of 167 (13%) of these patients received a retrograde perfusion, while 1113 (87%) received antegrade perfusion. Logistic analysis was used to evaluate outcomes and risk factors for stroke. Treatment selection bias was controlled by constructing a propensity score from core patient characteristics. The propensity score was the probability of receiving retrograde perfusion and was included along with the comparison variable in the multivariable analyses of outcome. The overall frequency of in-hospital mortality was 1.1% (14/1280) and postoperative stroke was 1.6% (21/1280). After adjusting for the propensity score, RAP was associated with a higher incidence of stroke (5 vs 1%; P = 0.002), postoperative delirium (14 vs 5%, P = 0.001) and aortic dissection (1.7 vs 0%; P = 0.01). Multivariable regression analysis revealed that the use of retrograde perfusion was an independent risk factor for stroke [odds ratio (OR) 4.28; P = 0.02] and postoperative delirium (OR 3.51; P = 0.001). Minimally invasive mitral valve procedure can be performed with low morbidity and mortality. The use of retrograde perfusion is associated with a higher incidence of neurological complications and aortic dissection when compared with antegrade perfusion. Central aortic cannulation allows the avoidance of complications associated with retrograde perfusion while extending the suitability of minimally invasive mitral procedures also to those patients who have an absolute contraindication to femoral artery cannulation.