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BACKGROUND There is controversy surrounding the efficacy of sodium bicarbonate and N-acetylcysteine for the prevention of contrast nephropathy. OBJECTIVE To evaluate the effects of sodium bicarbonate and N-acetylcysteine, used together and alone, on the risk of contrast nephropathy. DESIGN AND INTERVENTION Individuals aged ≥17 years who received an intravenous contrast agent during the period 1 April 2004 to 30 May 2005 at the Mayo Clinic, Rochester, MN were included in this retrospective analysis if they had at least 1 serum creatinine value recorded within the 7 days before contrast administration and 1 value recorded within the 7 days after contrast administration. Administration of intravenous sodium bicarbonate or oral N-acetylcysteine within 48 h of contrast exposure was noted. A pre-exposure serum creatinine level >707 µmol/l (>8mg/dl), a history of dialysis, and use of sodium bicarbonate for continuous renal replacement therapy were exclusion criteria. OUTCOME MEASURE The primary end point, contrast nephropathy, was defined as an increase in serum creatinine level of ≥25% or >44 pmol/l (>0.5 mg/dl) within 7 days of contrast exposure. RESULTS Serum creatinine data were available for >90% of cases in which a prophylactic agent was used. After exclusion of 27,945 ineligible patients, 7,977 patients (11,516 contrast exposures) remained for analysis. Contrast nephropathy occurred in 1,343 cases of contrast exposure (11.7%). The rate of contrast nephropathy was 11% in the 'no treatment' group (i.e. patients who did not receive sodium bicarbonate or N-acetylcysteine; 10,411 exposures), 15% in the group that received both sodium bicarbonate and N-acetylcysteine (221 exposures), 15% in the group that received N-acetylcysteine only (616 exposures) and 31% in the sodium-bicarbonate-only group (268 exposures). Patients who received sodium bicarbonate or N-acetylcysteine (or both) were older and more likely to have comorbidities than patients who did not receive these agents; those who received sodium bicarbonate alone were younger and less likely to have comorbidities than those who received N-acetylcysteine alone. After adjustment for predictors of contrast nephropathy (including age, previous contrast exposure and diabetes mellitus), sodium bicarbonate alone was associated with a significantly increased risk of contrast nephropathy compared with no treatment (odds ratio [OR] 3.10, 95% CI 2.28-4.18; P<0.001). This association persisted in a propensity scoring analysis, and when the cases were divided into subgroups on the basis of the particular sodium bicarbonate administration protocol used. N-acetylcysteine was not associated with any significant difference in the risk of contrast nephropathy, relative to no treatment, when used alone (OR 1.16, 95% CI 0.87-1.53; P=0.31) or with sodium bicarbonate (OR 1.07, 95% CI 0.68-1.65; P=0.75). Sodium bicarbonate alone was associated with a significantly higher adjusted risk of contrast nephropathy than N-acetylcysteine alone (OR 2.73, 95% CI 1.86-3.97; P<0.001). CONCLUSION The use of sodium bicarbonate for the prevention of contrast nephropathy should be reassessed. [ABSTRACT FROM AUTHOR]