BACKGROUND/AIM: Microscopic colitis is a known side-effect of proton pump inhibitors, but its association with the potassium-competitive acid blocker vonoprazan remains unclear. This study investigated this relationship, including the continued administration of vonoprazan after colitis onset. PATIENTS AND METHODS: Data from the first quarter of 2004 until the first quarter of 2024 in the Japanese Adverse Drug Event Report (JADER) database were analyzed. The reporting odds ratio (ROR) with its 95% confidence interval (CI) was calculated, and logistic regression analyses were performed. The proportion of patients with continued administration after onset was compared using Fisher's exact test with Bonferroni correction, and the administration duration was analyzed using the Steel-Dwass test. RESULTS: Among 1,523,914 adverse drug event reports from 921,160 cases, 751 reports of microscopic colitis were identified. Lansoprazole was the suspected cause in 481 reports (ROR=362, 95% CI=311-421), whereas vonoprazan appeared in 55 reports (ROR=33.5, 95% CI=25.4-44.1). Univariate and multivariate analyses yielded adjusted ORs of 2.56 (95% CI=2.23-2.93) and 2.87 (95% CI=2.48-3.31), respectively, for the association between vonoprazan and microscopic colitis. The time to onset of microscopic colitis in vonoprazan users ranged from 7 to 731 days (median=31 days). The proportion of reports in which lansoprazole and vonoprazan were continued after microscopic colitis onset was higher than that of vonoprazan continuation after drug eruption (. adverse cutaneous reactions). The duration of continued administration after microscopic colitis onset was longer than that after drug eruption. CONCLUSION: Using the JADER database, this study identified a safety signal for microscopic colitis associated with vonoprazan which is not listed in its package insert. Patients might continue vonoprazan after the onset of microscopic colitis. Although the database relies on spontaneous reporting, these findings warrant further investigation.