Introduction: The development of acute kidney injury (AKI) is associated with poor outcome. The modified RIFLE (risk, injury, failure, loss of kidney function, and end-stage renal failure) classification for AKI, which classifies patients with renal replacement therapy needs according to RIFLE failure class, improves the predictive value of AKI in patients undergoing cardiac surgery. Our aim was to assess risk factors for post-operative AKI and the impact of renal function on short- and long-term survival among all AKI subgroups using the modified RIFLE classification. Methods: We prospectively studied 2,940 consecutive cardiosurgical patients between January 2004 and July 2009. AKI was defined according to the modified RIFLE system. Pre-operative, operative and post-operative variables usually measured on and during admission, which included main outcomes, were recorded together with cardiac surgery scores and ICU scores. These data were evaluated for association with AKI and staging in the different RIFLE groups by means of multivariable analyses. Survival was analyzed via Kaplan-Meier and a risk-adjusted Cox proportional hazards regression model. A complete follow-up (mean 6.9 ± 4.3 years) was performed in 2,840 patients up to April 2013. Results: Of those patients studied, 14% (n = 409) were diagnosed with AKI. We identified one intra-operative (higher cardiopulmonary bypass time) and two post-operative (a longer need for vasoactive drugs and higher arterial lactate 24 hours after admission) predictors of AKI. The worst outcomes, including in-hospital mortality, were associated with the worst RIFLE class. Kaplan-Meier analysis showed survival of 74.9% in the RIFLE risk group, 42.9% in the RIFLE injury group and 22.3% in the RIFLE failure group (P <0.001). Classification at RIFLE injury (Hazard ratio (HR) = 2.347, 95% confidence interval (CI) 1.122 to 4.907, P = 0.023) and RIFLE failure (HR = 3.093, 95% CI 1.460 to 6.550, P = 0.003) were independent predictors for long-term patient mortality. Conclusions: AKI development after cardiac surgery is associated mainly with post-operative variables, which ultimately could lead to a worst RIFLE class. Staging at the RIFLE injury and RIFLE failure class is associated with higher short- and long-term mortality in our population.