Aim. Free radicals formed as the result of ischemic reperfusion injury contribute to renal damage in thoracoabdominal aneurysm (TAAA) repair. The objective of this study was to test the effectiveness of N-acetylcysteine (NAC), a free radical scavenger, in reducing renal dysfunction in these patients. Methods. A cohort of 20 consecutive patients undergoing TAAA repair represented the treatment group. NAC, 600 mg, was administered per os or iv twice daily the day before and the day of surgery. Data regarding urea, creatinine, urine output, cointerventions and renal function were collected prospectively. The control group was a retrospective cohort of 20 consecutive patients. Emergency and thoracic aneurysms were excluded. A left ventricular assist device (LVAD) was used for TAAA type I, II and III, and the clampand-go technique for type IV (Crawford classification). A 40% increase in creatinine between baseline and postoperative day 3 was the primary outcome. Secondary outcomes explored dialysis requirements and the change in creatinine at days 3, 6 and 7 postoperatively. Results. The NAC and the control groups were matched for extent of aneurysm. Age, sex, and comorbidities were similar in the 2 groups. No statistically significant difference was observed in the primary outcome (absolute risk reduction [ARR] 20%; 95% Confidence Interval 6-44%; P=0.34). The difference in the absolute value of serum creatinine at baseline and at day 3 and day 7 between the 2 groups did not reach statistical significance, but displayed a trend toward lower values in the treatment group at day 7 (P=0.06). Serum creatinine level measured at peak and days 3, 6, and 7, show that creatinine rises after surgery with an effect which is statistically significant by repeated measure analysis of variance (P<0.0001). The time NAC treatment interaction is also significant (P=0.029), suggesting a protective effect of treatment with respect to the expected rise in serum creatinine. The ARR of temporary or chronic dialysis associated with NAC did not reach statistical significance (ARR 20%; P=0.12). Conclusion. NAC is promising as a renoprotective agent in TAAA repair. Further randomized studies are needed.