PurposeTo estimate the association between proton-pump inhibitor (PPI) use and hip fracture. MethodsWe conducted a case-control study of 6774 pairs of men aged 45 years or older, matched on age, race, and medical center. Cases sustained incident hip fractures in 1997–2006. Fracture date was index date for each case-control pair. PPI exposure was identified from electronic pharmacy records, 1991–2006. PPI use was measured as (1) ever versus never; (2) adherence; (3) duration; and (4) recentness. Omeprazole and pantoprazole were analyzed separately using conditional logistic regression, adjusted for comorbidities. Nonusers were the referent group. ResultsEight hundred ninety-six (13.2%) cases and 713 (10.5%) controls used omeprazole before index date (matched odds ratio [OR], 1.13; 95% confidence interval [CI], 1.01–1.27). Greatest adherence (medication possession ratio > 80%) (OR, 1.33; 95% CI, 1.09–1.62), highest tertile of duration (OR, 1.23; 95% CI, 1.02–1.48), and recent use (OR, 1.22; 95% CI, 1.02–1.47) were associated with hip fracture. Six hundred ninety-four (10.2%) cases and 576 (8.5%) controls had used pantoprazole (OR, 1.10; 95% CI, 0.97–1.24). Longest duration (OR, 1.25; 95% CI, 1.02–1.53) and most recent use (OR, 1.38; 95% CI, 1.12–1.71) were associated with hip fracture. Our study suggests that PPI use and hip fractures are associated, with risk increasing with longer duration and more recent use.