Objective: Non-critically ill perioperative patients exhibit lower gastrointestinal bleeding risks with more controllable risk factors than critically ill patients. However, the specific preventive medication design of proton pump inhibitors (PPIs) still requires more support. The aim of this study is to investigate whether mild patients with risk factors for concomitant medication can improve the prevention of gastrointestinal bleeding by increasing the frequency of administration. Methods: This study is a single-center, retrospective study through propensity score - matched cohort. From August 2022 to December 2023, we screened 1,057 patients using lansoprazole for injection with risk factors for developing stress ulcers. The postoperative changes in hemoglobin levels were employed to evaluate the severity of gastrointestinal hemorrhage following the exclusion of other potential etiologies contributing to bleeding. Results: Overall, dose escalation demonstrated a marginal association with reduced postoperative ulcer-related gastrointestinal bleeding (odds ratio [OR] 1.385; 95% confidence interval [CI], 0.76–2.52; p < 0.05). In subgroup analyses, younger patients (<65 years) (OR 2.463; 95% CI, 1.128–5.378; p < 0.05), and those without anticoagulant/antiplatelet therapy (AA) (OR 1.813; 95% CI, 0.796–4.128; p < 0.05) showed a potential and enhanced therapeutic response. Conclusions: The dosing frequency of PPIs may improve the prophylactic efficacy against gastrointestinal bleeding. However, it is not reasonable to draw a conclusion that some combination of drugs will prioritize and directly increase the risk of gastrointestinal bleeding. For non-severe patients, the comprehensive risk assessment for ulcer development is methodologically more rigorous than relying exclusively on concomitant medication evaluation.