Prophylaxis of Pneumocystis pneumonia (PCP) with sulfamethoxazole-trimethoprim (SMX/TMP: ST) is required in patients with interstitial lung diseases who receive high-dose and long-duration corticosteroid therapy. One or two ST tablets (SMX 400 mg and TMP 80 mg/tablets) daily or two tablets three times weekly have been recommended as the regimen according to clinical trials for patients with human immunodeficiency virus infection. To clarify the optimal dosage of ST for prophylaxis of PCP in patients with interstitial lung diseases taking corticosteroids, we retrospectively analyzed 143 interstitial lung disease patients who had been treated with ST from April 2006 to August 2015. We compared the incidence of PCP and adverse events between two groups (one tablet daily group, n=47; one tablet twice-weekly group, n=68). PCP had not occurred in either group. However, the frequency of adverse events in the one tablet twice-weekly group was significantly lower than in the one tablet daily group (11.8% vs. 29.8%, p=0.016). In conclusion, as the prophylactic regimen with ST for against PCP, one tablet twice-weekly administration may be a sufficiently effective and well-tolerated regimen in interstitial lung disease patients taking corticosteroids therapy.