The mannose-binding lectin (MBL) pathway of complement is activated by pattern recognition. Genetic MBL variants are frequent and associated with low MBL serum levels. Higher MBL levels may be associated with more complement-mediated damage resulting in inferior graft survival. Pre-transplant serum samples from 266 consecutive deceased donor kidney transplant recipients were analyzed for MBL concentration by ELISA. Subsequently the cohort was analyzed for transplant-related outcome. There was no significant difference in incidence of delayed graft function in recipients with a low MBL level (< or =400 ng/mL) compared to those with a higher MBL level (>400 ng/mL) (37.1 vs. 34.9%). At 10 years, death-censored graft survival was 89.9% in patients with an MBL level below 400 ng/mL compared with 78.8% at a higher MBL level (p < 0.02). Multivariate analysis including traditional risk factors for graft loss showed an independent risk of 2.7 (95% CI 1.2-6.3) for death-censored graft loss if pre-transplant MBL levels were above 400 ng/mL. This difference was almost entirely explained by rejection-associated graft loss (2.4 vs. 12.4%, p < 0.01). Higher MBL levels seem to be associated with a more severe form of rejection leading to treatment failure and graft loss. If these data can be confirmed, pre-transplant MBL levels may provide additional information for risk stratification prior to kidney transplantation.