*Purpose: Although graft loss is a primary endpoint in many studies in kidney transplantation and a broad spectrum of risk factors has been identified, the eventual causes of graft failure in individual cases remain ill studied.

*Methods: We performed a cohort study in 1000 renal allograft recipients, transplanted between March 2004 and February 2013.

*Results: In total, 365 (36.5%) graft losses were identified, of which 211 (57.8%) were due to recipient death with a functioning graft and 154 (42.2%) to graft failure defined as return to dialysis or retransplantation. The main causes of recipient death were malignancy, infections and cardiovascular disease. The main causes of graft failure were distinct for early failures, where structural issues and primary nonfunction prevailed, compared to later failures with a shift towards chronic injury. In contrast to the main focus of current research efforts, pure alloimmune causes accounted for only 14.9% of graft failures and only 6.3% of overall graft losses.

*Conclusions: In conclusion, this study provides novel insight in the eventual causes of graft failure, and their relative contribution, highlighting the weight of nonimmune causes. Future efforts aimed to improve outcome after kidney transplantation should align with the relative weight and expected impact of targeting these causes.

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