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Abstract Background Antegrade cerebral perfusion (ACP), including unilateral and bilateral, is most commonly used for cerebral protection in aortic surgery. There is still no consensus on the superiority of the two methods. Our research aimed to investigate the clinical effects of u-ACP and b-ACP. Methods 321 of 356 patients with type A aortic dissection were studied retrospectively. 124 patients (38.6%) received u-ACP, and 197 patients (61.4%) received b-ACP. We compared the incidence of postoperative neurological complications and other collected data between two groups. Besides, we also analyzed perioperative variables to find the potential associated factors for neurological dysfunction (ND). Results For u-ACP group, 54 patients (43.5%) had postoperative neurological complications, including 22 patients (17.7%) with permanent neurologic dysfunction (PND) and 32 patients (25.8%) with temporary neurologic dysfunction (TND). For b-ACP group, 47 patients (23.8%) experienced postoperative neurological complications, including 16 patients (8.1%) of PND and 31 patients (15.7%) of TND. The incidence of PND and TND were significantly different between two groups along with shorter CPB time (p = 0.016), higher nasopharyngeal temperature (p≦0.000), shorter ventilation time (p = 0.018), and lower incidence of hypoxia (p = 0.022). Furthermore, multivariate stepwise logistic regression analysis confirmed that preoperative neurological dysfunction (OR = 1.20, p = 0.028), CPB duration (OR = 3.21, p = 0.002), and type of cerebral perfusion (OR = 1.48, p = 0.017) were strongly associated with postoperative ND. Conclusions In our study, it was observed that b-ACP procedure exhibited shorter CPB time, milder hypothermia, shorter ventilation time, lower incidence of postoperative hypoxia, and neurological dysfunction compared to u-ACP. Meanwhile, the incidence of ND was independently associated with three factors: preoperative neurological dysfunction, CPB time, and type of cerebral perfusion.