Stroke patients are at high risk of developing pneumonia, which is major cause of post-stroke mortality. Proton pump inhibitors and H 2 receptor antagonists are anti-ulcer drugs, which may predispose to the development of pneumonia by suppression of the gastric acid with bactericidal activity. Unlike proton pump inhibitors and H 2 receptor antagonists, mucoprotective agents have gastroprotective effects with no or less anti-acid property. We aimed to investigate effects of the acid-suppressive medications (proton pump inhibitors and H 2 receptor antagonists) and mucoprotective agents on risk for post-stroke pneumonia using the National Health Insurance Service-National Sample Cohort in Korea. This retrospective cohort study included 8,319 patients with acute ischemic stroke. Use of proton pump inhibitors, H 2 receptor antagonists, and mucoprotective agents (rebamipide, teprenone, irsogladine, ecabet, polaprezinc, sofalcone, sucralfate, and misoprostol) after stroke were determined based on the prescription records, which were treated as time-dependent variables. Primary outcome was the development of post-stroke pneumonia. During the mean follow-up period of 3.95 years after stroke, 2,035 (24.5%) patients had pneumonia. In the multivariate time-dependent Cox regression analyses (adjusted hazard ratio [95% confidence interval]), there was significantly increased risk for pneumonia with use of proton pump inhibitors (1.56 [1.24–1.96]) and H 2 receptor antagonists (1.40 [1.25–1.58]). In contrast to the proton pump inhibitors and H 2 receptor antagonists, use of mucoprotective agents did not significantly increase the risk for pneumonia (0.89 [0.78–1.01]). In conclusion, the treatment with proton pump inhibitors and H 2 receptor antagonists was associated with increased risk for pneumonia in stroke patients. Clinicians should use caution in prescribing the acid-suppressive medications for the stroke patients at great risk for pneumonia.