Objective: To determine whether computer-assisted prescription writing reduces the frequency of prescription errors in the emergency department (ED). Methods: A pre—post retrospective analysis was used to compare errors between handwritten (HW) and computer-assisted (CA) ED prescriptions. Prescriptions were reviewed for pharmacist clarifications. A clarification was defined as an error if missing information, incorrect information, incorrect dose, non-formulary medication, or illegibility was the reason for clarification. The HW and CA error rates were compared using odds ratios (ORs) with 95% confidence intervals (95% CIs). Results: During the pre-intervention period, there were 7,036 patient visits with 2,326 HW ED prescriptions filled for 1,459 patients. There were 91 clarifications, with a rate of 3.9%. There were 54 HW errors, for an error rate of 2.3%. During the post-intervention period, there were 7,845 patient visits with 1,594 CA prescriptions filled for 1,056 patients. There were 13 clarifications, with a clarification rate of 0.8%, and 11 errors, for a CA error rate of 0.7%. The CA prescriptions were substantially less likely to contain an error [OR 0.31 (95% CI = 0.10 to 0.36)] or to require pharmacist clarification [OR 0.19 (95% CI = 0.10 to 0.36)] than were the HW prescriptions. Conclusions: Computer-assisted prescriptions were more than three times less likely to contain errors and five times less likely to require pharmacist clarification than handwritten prescriptions.