Post-cardiac surgery acute kidney injury (AKI) is common and is associated with a significant increase in morbidity and mortality. We aimed to systematically review randomised trials that assessed the renoprotective utility of pharmacological agents in patients undergoing cardiac surgery. We searched PubMed, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials comparing renoprotective pharmacological interventions with control in adult patients undergoing cardiac surgery with cardiopulmonary bypass. We extracted data for mortality, need for renal replacement therapy (RRT), incidence of AKI, and creatinine clearance at 24-48 h. About 49 randomised controlled trials involving 4605 patients were included. Pharmacological interventions included dopamine, fenoldopam, calcium channel antagonists, natriuretic peptides, diuretics, and N-acetylcysteine. Most trials were of poor quality, with small sample sizes, under-reporting of randomisation procedure, allocation concealment and method of blinding. No pharmacological intervention significantly reduced mortality. Fenoldopam and Atrial Natriuretic Peptide (ANP) reduced the need for renal replacement therapy by 5% (NNT 20, 95% CI 11.3, 83.0) and 3.5% (NNT 29, 95% CI 17.1, 84.4), respectively. Brain Natriuretic Peptide resulted in a 10% reduction in the incidence of AKI (NNT 11, 95% CI 6.2, 32.0). Dopamine caused a significant reduction in creatinine clearance (-4.26 ml/min, 95% CI -7.14, -1.39). The quality of studies that have assessed pharmacological renoprotective agents in cardiac surgery is generally poor. Fenoldopam, ANP and BNP show evidence of renoprotection. Randomised studies evaluating the effect of novel renoprotective agents that are powered to detect clinically relevant differences in outcomes are required.