IntroductionDespite global concerns about the safety and quality of health care, population-wide studies of hospital outcomes are uncommon. The SAFety, Effectiveness of care and Resource use among Australian Hospitals (SAFER Hospitals) study seeks to estimate the incidence of serious adverse events, mortality, unplanned rehospitalisations and direct costs following hospital encounters using nationwide data, and to assess the variation and trends in these outcomes.Methods and analysisSAFER Hospitals is a cohort study with retrospective and prospective components. The retrospective component uses data from 2012 to 2018 on all hospitalised patients age ≥18 years included in each State and Territories’ Admitted Patient Collections. These routinely collected datasets record every hospital encounter from all public and most private hospitals using a standardised set of variables including patient demographics, primary and secondary diagnoses, procedures and patient status at discharge. The study outcomes are deaths, adverse events, readmissions and emergency care visits. Hospitalisation data will be linked to subsequent hospitalisations and each region’s Emergency Department Data Collections and Death Registries to assess readmissions, emergency care encounters and deaths after discharge. Direct hospital costs associated with adverse outcomes will be estimated using data from the National Cost Data Collection. Variation in these outcomes among hospitals will be assessed adjusting for differences in hospitals’ case-mix. The prospective component of the study will evaluate the temporal change in outcomes every 4 years from 2019 until 2030.Ethics and disseminationHuman Research Ethics Committees of the respective Australian states and territories provided ethical approval to conduct this study. A waiver of informed consent was granted for the use of de-identified patient data. Study findings will be disseminated via presentations at conferences and publications in peer-reviewed journals.