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Objective To evaluate co-prescribing of sedatives hypnotics and opioids.Design Retrospective study evaluating the association of patient characteristics and comorbidities with coprescribing.Setting and participants Using the national Merative MarketScan Database between 2005 and 2018, we identified patients who received an incident sedative prescription with or without subsequent, incident opioid prescriptions within a year of the sedative prescription in the USA.Outcome measures Coprescription of sedative-hypnotics and opioids.Results A total of 2 632 622 patients (mean (SD) age, 43.2 (12.34) years; 1 297 356 (62.5%) female) received incident prescriptions for sedatives over the course of the study period. The largest proportion of sedative prescribing included benzodiazepines (71.1%); however, z-drugs (19.9%) and barbiturates (9%) were also common. About 557 845 (21.2%) patients with incident sedatives also received incident opioid prescriptions. About 59.2% of these coprescribed patients received opioids coprescription on the same day. Multivariate logistic regression findings showed that individuals with a comorbidity index score of 1, 2 or ≥3 (aOR 1.19 (95% CI 1.17 to 1.21), 1.17 (95% C 1.14 to 1.19) and 1.25 (95% C 1.2 to 1.31)) and substance use disorder (1.21 (95% C 1.19 to 1.23)) were more likely to be coprescribed opioids and sedatives. The likelihood of receiving both opioid and sedative prescriptions was lower for female patients (aOR 0.93; 95% CI 0.92 to 0.94), and those receiving a barbiturate (aOR 0.3; 95% CI 0.29 to 0.31) or z-drugs (aOR 0.67; 95% CI 0.66 to 0.68) prescriptions at the index date.Conclusions Coprescription of sedatives with opioids was associated with the presence of comorbidities and substance use disorder, gender and types of sedatives prescribed at the index date. Additionally, more than half of the coprescribing occurred on the same day which warrants further evaluation of current prescribing and dispensing best practice guidelines.