Co-administration of methotrexate (MTX) and proton pump inhibitors (PPIs) is reported to increase serum MTX concentrations in patients receiving high-dose MTX therapy. However, the range of MTX high dosage is wide. We attempted to clarify the effects of PPIs co-administration on the elimination of MTX at the fixed dose of 1 g/m 2 in a retrospective cohort study of 46 patients with hematological malignancies who underwent a total of 91 cycles of chemotherapy. Data on gender, age, concomitant drugs, and laboratory test results were analyzed. The median and first to third quartile of MTX concentrations with and without PPI co-administration at 24, 48, and 72 h postdosing were 17.