question: Abstract Background Chloroquine or hydroxychloroquine (chloroquine) plus azithromycin is considered as therapy for COVID19. With benefit evaluations underway, safety concerns due to potential additive effects on QTc prolongation should be addressed. Objective We compared risk of cardiac adverse events between combinations of chloroquine and azithromycin and chloroquine and amoxicillin. Methods We conducted a retrospective cohort study using the IBM MarketScan Commercial Claims and Medicare Supplemental Databases, 2005–2018. We included autoimmune disease patients aged ≥18 years initiating azithromycin or amoxicillin for ≥5 days during chloroquine treatment. Patients had continuous insurance coverage ≥6 months before combination use until 5 days thereafter or inpatient death. Two outcomes were sudden cardiac arrest/ventricular arrhythmias (SCA/VA) and cardiac symptoms. We followed patients for up to 5 days to estimate hazard ratios (HR). Covariates were adjusted using stabilized inverse probability treatment weighting. Results We identified two SVC/VA events among >145,000 combination users. The adjusted incidence of cardiac symptoms among azithromycin and amoxicillin users was 276 vs 254 per 10,000 person-years with an adjusted HR of 1.10 (95%CI, 0.62–1.95). Conclusion Combination use of chloroquine and azithromycin at routine doses did not show pronounced increases in arrhythmias in this real-world population, though small sample size and outcome rates limit conclusions.