BACKGROUND Concern regarding the QTc interval in human immunodeficiency virus (HIV)-infected patients has been growing in recent years, and cases of prolonged QTc interval and torsades de pointes have been described in HIV-infected patients on methadone therapy. This study aimed to determine the prevalence and factors associated with long QTc interval in a cohort of opioid-dependent HIV-infected patients on methadone maintenance therapy. METHODS A cross-sectional study was conducted in opioid-dependent HIV-infected patients on methadone maintenance therapy at a drug abuse outpatient center. Patients with any cardiac disease, drug-positive urine test, electrolyte abnormalities, and changes in their antiretroviral therapy (ART) or methadone doses in the last 2 months were excluded. Heart rate and QT interval in lead II were measured using the Bazett formula. RESULTS Ninety-one patients were included: 58 (63.7%) were men with a median age of 44.5 years and 68 of 91 (74.7%) were on ART. Median methadone dose was 70 mg/day (range 15-250 mg/day) and mean QTc interval was 438 ± 34 ms. Prolonged QTc interval (>450 ms) was documented in 33 of 91(36.3%) patients, and 3 of 91 (3.2%) had QTc >500 ms. On multiple linear regression analysis, methadone doses (P = .005), chronic hepatitis C-induced cirrhosis (P = .008), and being ART-naive (P = .036) were predictive of prolonged QTc. CONCLUSIONS The prevalence of prolonged QTc interval in opioid-dependent HIV-infected patients on methadone maintenance therapy is high. Risk factors for prolongation of the QTc interval are chronic hepatitis C-induced cirrhosis, higher methadone doses, and being ART-naive. Thus, electrocardiographic monitoring is required to minimize cardiovascular morbidity and mortality in this specific HIV group.