Most episodes of acute rejection will resolve after steroid therapy without detrimental consequences on the liver allograft. However, steroid-resistant acute rejection may induce irreversible lesions of the graft and is associated with an increased risk of chronic rejection. The aim of this study was to determine whether there were predictive factors for steroid-resistant acute rejection after liver transplantation. A total of 108 adult liver recipients with a follow-up of at least 2 years have been analyzed; sixty-two (57%) patients had at least one episode of acute rejection. The rates of steroid resistance were 35%, 52% and 83% after a first (n = 62), second (n = 25), or third (n = 7) episode of acute rejection, respectively. Steroid resistance of acute rejection was significantly associated with a past history of pretransplant steroid therapy (P = 0.004). High levels of ALT (P = 0.03) and serum bilirubin (P = 0.002) were also predictive of steroid-resistant acute rejection. Eight (7%) patients eventually developed chronic rejection. Predictive factors for chronic rejection included steroid-resistant acute rejection (P = 0.01), recurrent acute rejection (P = 0.03), and CMV infection (P = 0.01). In conclusion, this study suggests that pretransplant steroid administration or high levels of ALT and bilirubin in rejecting patients are risk factors for steroid resistance and should lead to aggressive antirejection therapy without delay.