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Aim: Association between C4d deposition and renal allograft survival is still uncertain. We retrospectively evaluated the clinical outcome of C4d deposition in allograft renal biopsies. Methods: One hundred and fifty biopsies from 150 patients with a histological diagnosis of acute rejection from December 1997 to March 2007 were included. Paraffin-embedded sections were stained with a polyclonal antibody using an immunoperoxidase technique. Detailed clinical data were obtained by retrospective review. Results: C4d was stained positively in 74 (49.3%) of 150 cases: 47 (61.5%) biopsies showed diffuse C4d deposition and 27 (38.5%) showed focal C4d deposition. During follow up, significantly more C4d-positive patients (24/74 patients, 32.4%) lost their grafts, compared with the C4d-negative group (10/76 patients, 13.2%) ( P = 0.005). After a Kaplan–Meier analysis, grafts from the C4d-negative group had a markedly higher survival as compared with the C4d-positive group ( P = 0.003, log–rank test). Graft survival among C4d-negative, C4d diffuse-positive, and C4d focal-positive groups was significantly different ( P = 0.007, log–rank test). The graft survival rate among C4d-negative patients in early (<6 months) and later biopsies (>6 months), and C4d-positive patients in early and in later biopsies was different ( P = 0.028, log–rank test). The adjusted risk ratio of graft failure after Cox proportional hazards multivariate analyses for C4d-positive patients was 3.309 (95% confidence interval, 1.413–6.537; P = 0.004). Conclusion: Patients with C4d deposition had an inferior graft survival, especially with diffused C4d deposition, and later experienced acute rejection. C4d deposition was an independent risk factor for graft survival. [ABSTRACT FROM AUTHOR]