OBJECTIVES: Cerebral protection during acute aortic dissection Type A (AADA) surgery may be affected by perfusion strategies and ischaemic protective drugs. METHODS: We analysed the impact of intraoperative barbiturate, steroid and mannitol use and adjunctive cerebral perfusion (CP), on 30-day mortality and new postoperative mortality-corrected permanent neurological dysfunction (PNDmc) in the German Registry for Acute Aortic Dissection Type A. RESULTS: Two thousand one hundred and thirty-seven AADA patients were registered over a 4-year period. The overall 30-day mortality was 16.9%, and the overall rate of PNDmc was 10.0%. A total of 48% of patients received no neuroprotective drugs (control group), steroid monotherapy was used in 11.2% of patients, barbiturates in 8.4%, mannitol in 7.3% and the remainder (25.1%) received a combination of these drugs. The PNDmc rate was 10.6% in the control group and lower (7.1%) in the steroid group (adjusted odds ratio [OR] 0.50; 95% confidence interval [95% CI] 0.24-0.96; P = 0.049). No PNDmc reduction was observed for mannitol or barbiturates. Thirty-day mortality was 18.7% in the control group and with 8.9% lower (P = 0.003) in the mannitol group (adjusted OR 0.58; 95% CI 0.19-1.49; P = 0.295). Hypothermic circulatory arrest that exceeded 30 min was associated with an increased 30-day mortality rate (31.4%) compared with patients who received adjunctive CP >30 min during aortic arch intervention (21.4%) (P = 0.04). We were unable to demonstrate a significant protective effect of any neuroprotective drug on 30-day mortality, or PNDmc rates during prolonged (≥30 min) cerebral ischaemia. CONCLUSION: Mannitol may be associated with decreased mortality in patients undergoing AADA surgery. Steroid administration may be associated with improved neurological outcomes, but more investigation is required.