The correlation between hip replacement (Hip-Repl) and chronic osteomyelitis (COM) has not been studied in Asian populations. Thus, we assessed Hip-Repl-related risk of developing COM via a population-based, nationwide, retrospective cohort study. The Hip-Repl cohort was obtained from Taiwan's Longitudinal Health Insurance Database 2000, and included patients who underwent Hip-Repl between 2000 and 2010; the control cohort was also selected from this database. Patients with a history of COM were excluded in both cohorts. We used univariate and multivariate Cox proportional hazards regression models to calculate the adjusted hazard ratios (aHRs) by age, sex, and comorbidities for developing COM. A total of 5349 patients who received a Hip-Repl and 10,372 matched controls were enrolled. In the Hip-Repl group, the risk for COM was 4.18-fold [95 % confidence interval (CI) = 2.24-7.80] higher than that in the control group after adjustment. For patients aged ≤65 years, the risk was 10.0-fold higher (95 % CI = 2.89-34.6). Furthermore, the risk was higher in the Hip-Repl cohort than in the non-Hip-Repl cohort, for both patients without comorbidity (aHR = 16.5, 95 % CI = 2.07-132.3) and those with comorbidity (aHR = 3.49, 95 % CI = 1.78-6.83). The impact of Hip-Repl on the risk for COM was greater among patients not using immunosuppressive drugs, and occurred during the first postoperative year. Patients who received Hip-Repl have an increased risk of developing COM. This risk was higher among males and patients aged 65 years or younger, and during the first postoperative year.