Under- or overdosing of N-acetylcysteine (NAC), when used to treat paracetamol toxicity, is associated with significant morbidity and mortality. This study evaluated the effect of a weight-based dosing chart (WBDC) introduced to decrease NAC prescription errors. We undertook a pre- and post-intervention trial in a single ED. The intervention (the NAC WBDC) was introduced in January 2011 and publicised by posters and presentations at medical handovers and education sessions. ED staff were not aware that use of the WBDC was to be evaluated. Data were collected using a retrospective explicit medical record review by a single investigator. The study end-point was the proportion of NAC prescriptions with errors. The 81 and 42 patients enrolled in the pre- and post-intervention periods, respectively, did not differ in age, sex or weight (P > 0.05). Post-intervention, there were significant reductions in prescription errors of fluid type/volume (50.6% vs 4.8%, P < 0.001), NAC dosage (13.6% vs 0.0%, P = 0.01) and infusion rate (11.1% vs 0.0%, P = 0.03). The proportion of prescriptions with any errors also decreased (56.8% vs 14.3%, P < 0.001). However, there were no improvements in the documentation of patient weight (65.4% vs 64.3%, respectively, P = 0.90) or the proportion of incomplete prescriptions (4.9% vs 11.9%, P = 0.16). The introduction of a WBDC did not produce a clinically significant reduction in major NAC prescription error rates (as pre-defined in this study); however, there was a clear trend towards a reduction. The WBDC significantly reduced total and minor NAC prescription error rates.