The significance of C4d‐Banff scores in protocol biopsies of kidney transplant recipients with preformed donor‐specific antibodies (DSA) has not been determined. We reviewed 157 protocol biopsies from 80 DSA+ patients obtained at 3 months and 1 year post‐transplant. The C4d Banff scores (1,2,3) were associated with significant increments of microcirculation inflammation (MI) at both 3 months and 1 year post‐transplant, worse transplant glomerulopathy and higher class II DSA‐MFI (p < 0.01). Minimal‐C4d had injury intermediate between negative and focal, while focal and diffuse‐C4d had the same degree of microvascular injury. A total of 54% of patients had variation of C4d score between 3 months and 1 year post‐transplant. Cumulative (3 month + 1 year) C4d scores correlated with long‐term renal function worsening (p = 0.006). However, C4d staining was not a sensitive indicator of parenchymal disease, 55% of C4d‐negative biopsies having evidence of concomitant MI. Multivariate analysis demonstrated that the presence of MI and class II DSA at 3 months were associated with a fourfold increased risk of progression to chronic antibody‐mediated rejection independently of C4d (p < 0.05). In conclusion, the substantial fluctuation of C4d status in the first year post‐transplant reflects a dynamic humoral process. However, C4d may not be a sufficiently sensitive indicator of activity, MI and DSA being more robust predictors of bad outcome.