Background: Gastric and duodenal ulcerations are common during multiple-dosing aspirin treatment, such as for prevention of cardiovascular disease. On capsule endoscopy, oral administration of the bacterial strain Bifidobacterium breve Bif195 (DSM 33360) reduced the risk of aspirin-induced small intestinal damage, without affecting cyclo-oxygenase-2 (COX-2) inhibition. Aim: To evaluate endoscopically the effect of Bif195 on aspirin-induced stomach and duodenal mucosal damage. Methods: Twenty-five healthy volunteers underwent two intervention periods in a randomised, double-blind, placebo-controlled crossover design including four gastroduodenoscopies and 6 weeks washout. Each intervention was a 4-week oral co-treatment of aspirin 300 mg daily and Bif195 (≥10¹¹ colony-forming units daily) or placebo. Primary endpoint was change in Lanza score - ranging from 0 (normal mucosa) to 4 (>10 erosions or ulcer). Results: All 25 participants (56% females); age 27.3 (±4.8) years; BMI 23.2 (±3.4) kg/m², completed the trial exhibiting significant increases in Lanza scores during placebo treatment as compared to baseline. Bif195 reduced gastric Lanza score with an odds ratio of 7.2 (95% confidence interval 1.72–30.08, p = 0.009) compared to placebo with no related adverse events. There were no significant changes in Lanza scores in the duodenum. Conclusions: Bif195 reduces aspirin-induced gastric mucosal damage and may serve as a safe supplement during multiple-dosing aspirin treatment.