Harms related to prescription opioid use are an ongoing patient safety challenge. Based on data from one hospital between 2014 and 2016, this cohort study found that nearly 50% of hospitalized patients were discharged with an opioid prescription, and 80% of those prescriptions were among patients discharged from a surgical unit. Opioid-related medication errors were more common in handwritten discharge prescriptions compared to electronic prescriptions; electronic prescriptions were associated with a 69% lower risk of opioid-related medication errors.