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Recent studies using histology alone in select patients have suggested thatHelicobacter pylori-negative gastritis may be common. The objective of this study was to investigate the prevalence ofH. pyloriamong individuals with histologic gastritis.Subjects between 40 and 80 years underwent elective esophagogastroduodenoscopy at a VA Medical Center. Gastric biopsies were mapped from seven prespecified sites (two antrum, four corpus, and one cardia) and graded by two gastrointestinal pathologists, using the Updated Sydney System.H. pylori-negative required four criteria: negative triple staining at all seven gastric sites, negativeH. pyloriculture, negative IgGH. pyloriserology, and no previous treatment forH. pylori. Data regarding tobacco smoking, alcohol drinking, nonsteroidal anti-inflammatory drug, and proton pump inhibitor (PPI) use were obtained by questionnaire.Of the 491 individuals enrolled, 40.7% (200) had gastritis of at least grade 2 in at least one biopsy site or grade 1 in at least two sites. Forty-one (20.5%) hadH. pylori-negative gastritis; most (30 or 73.2%) had chronic gastritis, five (12.2%) had active gastritis, and six (14.6%) had both.H. pylori-negative gastritis was approximately equally distributed in the antrum, corpus, and both antrum and corpus. Past and current PPI use was more frequent inH. pylori-negative vs.H. pylori-positive gastritis (68.2% and 53.8%;P=0.06).We used multiple methods to define non-H. pylorigastritis and found it in 21% of patients with histologic gastritis. While PPI use is a potential risk factor, the cause or implications of this entity are not known.