It is commonly accepted that the longer the time on extracorporeal cardiopulmonary bypass (CPB), the higher is the likelihood of developing acute renal failure requiring dialysis (ARF-D). Nonetheless, previous works elicited conflicting evidence. We investigated the relationship between CPB duration and ARF-D occurrence. Data were extracted from a large observational study. All factors independently associated with ARF-D were detected. Overall, 11,092 case record forms were analyzed. At the univariate analyses, time on CBP was associated with an increase in the ARF-D risk (odds ratio of fifth vs. first quintile of CBP time: 3.84; 95% confidence interval: 2.58–5.7; P < 0.001). However, after adjusting for confounders, the association between time on CBP and ARF-D lost its statistical significance. In this large dataset, CBP time did not predict ARF-D occurrence. These results might suggest that an accurate risk assessment might be more important than time on CPB in determining ARF-D occurrence.