Background Optimal hydration measures to prevent contrast-induced nephropathy are controversial. Study Design We conducted a systematic review and meta-analysis using the MEDLINE database (1966 to January 2008), EMBASE (January 2008), and abstracts from conference proceedings. Setting & Population Adult patients undergoing contrast procedures. Selection Criteria for Studies Randomized controlled trials comparing intravenous hydration with sodium bicarbonate with hydration with intravenous normal saline for prevention of contrast-induced nephropathy. Intervention Hydration with intravenous sodium bicarbonate with or without N -acetylcysteine versus hydration with normal saline with or without N -acetylcysteine. Outcomes Contrast-induced nephropathy, need for renal replacement therapy, and worsening of heart failure. Results Twelve trials (1,854 participants) were included. Sodium bicarbonate significantly decreased the risk of contrast-induced nephropathy (12 trials, 1,652 patients; odds ratio OR, 0.46; 95% confidence interval CI, 0.26 to 0.82; I2 = 55.9%) without a significant difference in need for renal replacement therapy (9 trials, 1,215 patients; OR, 0.50; 95% CI, 0.16 to 1.53; I2 = 0%), in-hospital mortality (11 trials, 1,640 patients; OR, 0.51; 95% CI, 0.15 to 1.69), or congestive heart failure compared with controls. Similar results were seen for the risk of contrast-induced nephropathy when sodium bicarbonate was compared with normal saline alone (OR, 0.39; 95% CI, 0.20 to 0.77), but not when sodium bicarbonate/ N -acetylcysteine combination was compared with N -acetylcysteine/normal saline combination (OR, 0.68; 95% CI, 0.34 to 1.37). A subgroup analysis limited to published trials showed similar results (OR, 0.26; 95% CI, 0.10 to 0.64; I2 = 63.3%), whereas unpublished studies showed a nonsignificant decrease (OR, 0.85; 95% CI, 0.46 to 1.57; I2 = 25.9%) in risk of contrast-induced nephropathy. Limitation Publication bias and heterogeneity. Conclusion Hydration with sodium bicarbonate decreases the incidence of contrast-induced nephropathy in comparison to hydration with normal saline without a significant difference in need for renal replacement therapy and in-hospital mortality. Larger studies analyzing patient-centered outcomes are needed.