Pyloric gland metaplasia (PGM) is a histopathologic change usually seen after inflammatory injury and, although described in association with inflammatory bowel disease (IBD) and particularly Crohn disease (CD), its significance is still debated. We evaluated long-term correlates of PGM in a large cohort of 601 intestinal specimens, 227 (37.8%) biopsies, and 374 (62.2%) resections, from 567 different patients, 328 (57.8%) male and 239 (42.2%) female, with a mean age of 43.4±15.8 years. During mean clinical follow-up of 83.5±48.1 months, 511 (90.1%) patients were diagnosed with IBD, 457 (89.4%) with CD, and 53 (10.4%) with ulcerative colitis. In multivariate analysis, IBD patients with PGM were younger (P<0.001) and more often had severely active inflammation (P=0.002) compared with non-IBD patients, whereas, among IBD patients, those with ulcerative colitis were more likely to have PGM in a biopsy (P<0.001) or in the colorectum (P=0.009), compared with CD patients. Kaplan-Meier analyses showed that incidental PGM in a biopsy was more likely to predict IBD in patients younger than 50 years (P<0.001) and those without a history of bowel surgery (P<0.001) and also more likely to signify CD in patients younger than 50 years (P=0.004), those without a history of bowel surgery (P=0.020), and when identified in the small intestine (P=0.032). In conclusion, intestinal PGM warrants a high suspicion for IBD and specifically CD, however, it should be interpreted with caution, especially in older patients or those with a history of prior intestinal surgery and in colorectal biopsies or specimens lacking severely active inflammation.