Co‐prescribing of opioids and sedatives is a known risk factor for opioid‐induced ventilatory impairment (OIVI). Prevalence data for sedative and opioid co‐prescription in inpatients in Australia are unknown. Our objective was to determine the prevalence of inpatient sedative and opioid co‐prescribing and to identify factors associated with co‐prescription. We conducted a retrospective cross‐sectional study from July 2017 to October 2017 across four South Australian hospitals utilizing a centralized electronic health record. Multivariate analysis was used to identify characteristics predictive of co‐prescribing of a strong opioid (fentanyl, hydromorphone, morphine, and oxycodone) and sedative medications (benzodiazepines, antiepileptics, antipsychotics, and tricyclic antidepressants). Of the 6170 inpatients, 2795 (45.3%) were prescribed a strong opioid and of those, 1889 (30.6% of all inpatients) were co‐prescribed a sedative. Of those prescribed a strong opioid, five (0.18%) developed OIVI. Patients prescribed a strong opioid had a 27–77% increased likelihood of being prescribed a sedative. Factors predictive of sedative co‐prescribing included the presence of disease of the central nervous system adjusted OR (aOR) 8.66 [95% CI 5.83–12.9] and respiratory disease aOR 1.42 [95% CI 1.17–1.72]. Nearly, one third of all hospital inpatients were co‐prescribed a strong opioid and a sedative medication. Patients with comorbidities resulting in increased risk of respiratory depression/OIVI were more likely to have sedative co‐prescription. Clinicians should be aware of the effects of high‐risk medications and ensure that systems and monitoring are in place that help mitigate adverse outcomes.