Background and Aims: A considerable number of au-toimmune hepatitis (AIH) patients completely or partially fail on first-line treatment. Several studies on the use of calcineurin inhibitors (CNIs) in the treatment of AIH have been published without focusing on indication. The aim was to assess the efficacy of CNIs in the treatment of adult AIH patients, specifically focusing on indication: first-line intolerant and with first-line insufficient response (failure to achieve or maintain remission), and with second versus third-line treatment. Methods: A literature search included studies on the use of CNIs in adult AIH. Patients with past or present use of CNIs from the Dutch AIH group cohort were added. The primary endpoint was biochemical remission while using CNIs. Secondary endpoints were biochemical response, treatment failure, and adverse effects. Results: Twenty studies from the literature and nine Dutch patients were included describing the use of cyclosporine in 59 and tacrolimus in 219 adult AIH patients. The CNI remission rate was 53% in patients with insufficient response to first-line treatment and 67% in patients intolerant to first-line treat-ment. CNIs were used as second-line treatment in 73% with a remission rate of 52% and as third-line treatment in 22% with a remission rate of 26%. Cyclosporine was discontin-ued in 13% and tacrolimus in 11% of patients because of adverse events. Conclusions: CNIs as rescue treatment in adult AIH patients are reasonably effective and safe both with insufficient response or intolerance to previous treat-ment. Prospective studies are needed.