Intravenous sodium bicarbonate has been proposed to reduce the risk for contrast-induced nephropathy (CIN). To determine the effect of sodium bicarbonate on the risk for CIN. MEDLINE, PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials from 1950 to December 2008; conference proceedings; and ClinicalTrials.gov, without language restriction. Randomized, controlled trials of intravenous sodium bicarbonate that prespecified the outcome of CIN as a 25% increase in baseline serum creatinine level or an absolute increase of 44 micromol/L (0.5 mg/dL) after radiocontrast administration. Using standardized protocols, 2 reviewers serially abstracted data for each study. 23 published and unpublished trials with information on 3563 patients and 396 CIN events were included. The pooled relative risk was 0.62 (95% CI, 0.45 to 0.86), with evidence of significant heterogeneity across studies (I(2) = 49.1%; P = 0.004). Some heterogeneity was due to the difference in the estimates between published and unpublished studies: relative risk, 0.43 (CI, 0.25 to 0.75) versus 0.78 (CI, 0.52 to 1.17), respectively. Meta-regression showed that small, poor-quality studies that assessed outcomes soon after radiocontrast administration were more likely to suggest benefit (P < 0.05 for all). No clear effects of treatment on the risk for dialysis, heart failure, and total mortality were identified. Power to assess clinical end points was limited. The effectiveness of sodium bicarbonate treatment to prevent CIN in high-risk patients remains uncertain. Earlier reports probably overestimated the magnitude of any benefit, whereas larger, more recent trials have had neutral results. Large multicenter trials are required to clarify whether sodium bicarbonate has value for prevention of CIN before routine use can be recommended. None.