Objective To evaluate the efficacy and safety of rabeprazole coadministration with low-dose aspirin (LDA). Methods From 2015 to 2018, we conducted a large-scale, multicenter, prospective observational study to assess the safety and efficacy of treatment with rabeprazole (5 or 10 mg/day) in combination with LDA. Results The incidence of adverse reactions was 0.73% (11/1,513 patients), with no serious adverse reactions. We found no trend toward increases in the incidence of adverse reactions with increases in treatment duration. The cumulative recurrence rate of ulcers by Week 52 (Kaplan-Meier estimates) was 3.50% (range, 1.56-7.75%). No gastrointestinal bleeding was reported. Conclusion Rabeprazole in combination with LDA appears as safe and effective in real-world situations as in clinical trials.