Contrast-induced nephropathy (CIN) is a form of acute kidney injury and a significant source of morbidity and mortality. We defined CIN as an increase in serum creatinine (SCr) of 25% or more within 48 hours of receiving contrast. We retrospectively compared sodium bicarbonate with normal saline for prevention of CIN. One hundred and eighty-seven patients exposed to contrast during cardiac angiography, treated prophylactically either with sodium bicarbonate (n = 89) or with normal saline (n = 98), were studied. Baseline characteristics of both groups were similar in terms of age, amount of contrast, presence of diabetes mellitus, and use of furosemide and angiotensin-converting enzyme inhibitor. Patients in bicarbonate group had more severe renal disease with higher baseline SCr (1.58 +/- 0.5 mg/dL vs. 1.28 +/- 0.3 mg/dL, p = 0.001) and lower estimated glomerular filtration rate (eGFR, 51.06 +/- 14.0 mL/min vs. 62.3+/-13.5 mL/min, p = 0.001) compared to the normal saline group. After the contrast exposure, there was significant drop in eGFR (6.4%) and increase in SCr (11.3%) in the normal saline group and no significant change in the bicarbonate group. Three patients (3.4%) in the bicarbonate group as opposed to 14 patients (14.3%) in the normal saline group developed CIN (p = 0.011). Two patients in the normal saline group and none in the bicarbonate group needed dialysis. There was no significant difference in serum creatinine at three-month follow-up in either group. The above findings suggest that hydration with intravenous sodium bicarbonate is more effective than normal saline in preventing contrast-induced nephropathy.