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OBJECTIVES: People who inject drugs (PWID) have poor oral health. However, their oral health-related quality of life (OHRQoL) is unknown. Our study was designed to measure the OHRQoL of PWID. METHODS: The Oral Health Impact Profile-14 (OHIP-14) was administered to 794 PWID recruited in Australian capital cities as part of the 2013 Illicit Drug Reporting System (IDRS). Three OHIP-14 summary indicators were examined: “Prevalence” (proportion reporting >/=1 item at least “fairly often”), “severity” (mean total OHIP-14 score), and “extent” (number of impacts reported at least “fairly often”). Associations between “prevalence” and “extent” and variables drawn from the health, drug use, and social domains were investigated. RESULTS: All OHIP-14 summary indicators among IDRS participants were significantly higher than in the general Australian population. In multivariate analysis, the “prevalence” indicator was significantly and positively associated with female gender [adjusted odds ratio (AOR) = 1.75, 95% CI 1.27-2.38], those born in Australia (AOR = 2, 95% CI 1.25-3.23), not completing Year 10 compared with those who had completed Year 12 or a higher qualification (AOR = 1.59, 95% CI 1.03-2.44), and methadone treatment (AOR = 1.61, 95% CI 1.14-2.29). The “extent” indicator was significantly and positively associated with female gender [adjusted incidence rate ratio (AIRR) = 1.56, 95% CI 1.19-2.08], unemployment (AIRR = 1.59, 95% CI 1.01-2.44), and having an injecting career of 10-20 years (AIRR = 1.76, 95% CI 1.03-3.01). CONCLUSIONS: PWID have poorer OHRQoL than the Australian general population. Poor OHRQoL was particularly common in female PWID and those with longer injecting careers. Interventions to improve the oral health of PWID may improve their OHRQoL.