Several definitions have been used to assess rates of contrast-induced nephropathy (CIN) in patients undergoing percutaneous coronary intervention (PCI). Whether the definition influences observed rates of CIN is unclear. The Oxilan Registry was the first-ever prospective analysis of the efficacy and safety of ioxilan (low-osmolar and low-viscosity contrast medium), including rates of CIN assessed by multiple definitions, in PCI. From July 2006 to June 2007, consecutive patients undergoing PCI using ioxilan were enrolled. Serum creatinine (SCr) and estimated glomerular filtration rate (eGFR) were assessed at baseline and 3 to 5 days after PCI. CIN was defined as SCr increase >or=0.5 mg/dl, eGFR decrease >or=25%, SCr increase >or=25%, or the composite. Of 400 patients (age 62 +/- 11 years), 19% were women, 37% were diabetic, 22% were anemic, and 8% had a history of congestive heart failure. Baseline SCr was 1.12 +/- 0.3 mg/dl and 24% had an eGFR <60 ml/min. CIN rates were 3.3% (SCr increase >or=0.5 mg/dl), 7.6% (eGFR decrease >or=25%), 10.2% (SCr increase >or=25%), and 10.5% (composite). Hospitalization was prolonged in 3.4% of patients with CIN and none required dialysis. There were no deaths or severe allergic reactions. Non-ST-elevation myocardial infarction and repeat revascularization each occurred in 0.8%. In conclusion, in this unselected population undergoing PCI, CIN ranged in frequency from 3.3% to 10.5% depending on the definition used and was not associated with in-hospital mortality or substantial morbidity, such as dialysis. The wide variation in CIN and its lack of association with adverse outcomes underscore the need for a standardized, clinically relevant definition.