Background Medication errors are a leading cause of harm to patients in hospital that can be decreased by electronic medication management systems. Aims This study determined the effects of electronic prescribing using the Enterprise Patient Administration System (EPAS) on prescribing errors and adverse drug reaction (ADR) documentation in South Australian public hospitals. Methods A prospective structured medication chart audit was conducted before (in 2012) and after the implementation (in Dec 2014) of EPAS, comparing the paper‐based National Inpatient Medication Chart (NIMC) with prescribing. All inpatients were eligible for inclusion in the study. Prescribing order errors were determined by the percentage of medication orders that had unclear, illegal or unsafe prescriptions. The quality of ADR documentation was assessed by the percentage of patients with correct documentation. Results The total number of prescribing errors before and after the implementation of EPAS was 67.7 and 2.8 per 100 orders, respectively. The frequency of prescribing order errors due to unclear, illegal and unsafe prescriptions decreased to almost zero with EPAS. Prescriptions classified as unsafe due to incorrect dose, route of administration or dosing frequency decreased from 5.8% to 0.03% of medication orders before versus after EPAS implementation (p < 0.0001). Completed ADR documentation was similar between the paper‐based NIMC and EPAS, but the percentage of patients with ADR alerts who required them was 100% in EPAS compared with 27% on the NIMC (p < 0.0001). Conclusions E‐prescribing using EPAS significantly decreased prescribing errors and increased ADR alerts. Continued implementation of electronic medication management systems is an important approach to improve medication safety.