BACKGROUND : Contrast induced nephropathy (CIN) is a common complication of procedures that foresee the use of contrast media. Several risk factors have been identified as independent predictors of CIN, but, to date, no definitive data are available about the association between the angiographic approach and its development. RESULTS : Our population included 4199 patients undergoing coronary angiography and/or PCI. CIN was defined as an absolute ≥0.5 mg/dl or a relative ≥25% increase in creatinine level at 24-48 h after the procedure without another clear cause for the acute kidney injury. The total incidence of CIN was 12.4%. We divided our population into two groups, according to the angiographic approach: transradial (TR) n = 1915 or transfemoral (TF) n = 2284. Patients treated with TR approach were more often males, with history of hypertension, and PCI, but less often diabetic, with previous myocardial infarction, coronary artery by-pass graft surgery and cerebrovascular accident. They had a higher ejection fraction, higher prevalence of PCI, elective indication but interestingly a lower amount of contrast volume. Patients treated with TR approach had higher platelets, Total, LDL and HDL cholesterol, but lower triglycerides, glycaemia and basal creatinine. No significant difference was observed between the two groups regarding the development of CIN (TR 13.2% vs TF 11.7%, p = 0.16). The absence of association between angiographic approach and the incidence of CIN was also confirmed at multivariate analysis after correction for baseline confounders (Adjusted OR [95% CI] = 1.2 [0.97-1.50], p = 0.09) and at subgroup analysis according to main risk factors for CIN. Similar results were obtained dividing our population according to propensity score tertiles: 1st Tertile CIN (TF 8.8% vs TR 8.9%), p = 0.95; OR (99% CI) = 1.01 (0.96-1.48), p = 0.95, 2nd Tertile CIN (TF 10.8% vs TR 12.4%), p = 0.35; OR (99% CI) = 1.17 (0.84-1.62), p = 0.35, and 3rd Tertile CIN (TF 15.6% vs TR 17.2%), p = 0.41; OR (99% CI) = 1.12 (0.85-1.48), p = 0.41. CONCLUSIONS : This is the first large study showing the absence of relationship between the angiographic access and the incidence of CIN.