Tacrolimus is the cornerstone of the therapeutic immunosuppressive strategy in liver transplantation. The inter‐individual and intra‐individual variability of its trough blood concentrations is a surrogated biomarker of allograft rejection. Here we described two cases of patients with liver transplant who exhibited increases of tacrolimus blood trough concentration adjusted on the dose while experiencing acute inflammatory episodes. These case reports highlight the inhibitory effect of acute inflammation on tacrolimus metabolism and show that it accounts for the longitudinal intra‐individual variability of tacrolimus blood concentrations, beyond drug–drug interaction and observance.