A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'does prophylactic administration of N-acetylcysteine (NAC) prevent acute kidney injury (AKI) following cardiac surgery?' More than 60 papers were found using the reported search, of which 10 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The administration of NAC prior intravenous radioactive contrast has been shown to reduce the incidence of contrast-induced nephropathy. There have been two recent meta-analyses and several randomised controlled trials (RCTs) and investigating the effectiveness of prophylactic administration of NAC in the prevention of AKI following cardiac surgery. The RCTs have investigated the use of NAC to prevent AKI in low-risk patients, high-risk patients and high-risk patients with pre-existing chronic kidney disease. The meta-analyses and RCTs demonstrated that the prophylactic administration of NAC did not reduced the incidence of AKI, postoperative complications, postoperative interventions, mortality or length of ICU stay. We conclude that prophylactic administration of NAC does not prevent AKI or reduce mortality following cardiac surgery.