At the American College of Gastroenterology 2025 Annual Scientific Meeting, researchers reported that adult males aged 60 and older taking phosphodiesterase-5 (PDE-5) inhibitors—such as sildenafil, tadalafil, or vardenafil—had significantly lower rates of gastric cancer compared with matched controls not using these medications. In this large retrospective cohort study of nearly 1.6 million patients, PDE-5 inhibitor use was also linked to reduced colon cancer risk. However, the protective effect did not extend to patients with Helicobacter pylori infection, who continued to face higher gastric cancer risk despite PDE-5 use. The findings support potential anti-neoplastic effects of PDE-5 inhibitors in gastrointestinal malignancies and underscore the need for prospective studies to clarify mechanisms and risk modulation in H. pylori–positive populations.