OBJECTIVES: This analysis was conducted as part of a federally funded national pilot to evaluate electronic prescribing in the community practice setting. The objective was to measure the incidence and nature of prescribing errors on e-prescriptions that required active intervention by dispensing pharmacists to correct. METHODS: A panel of participating pharmacists reported their Medication Therapy Interventions (MTI) using a standardized documentation protocol. RESULTS: Data were reported from 68 participating chain pharmacies in 5 states during 312 work shifts between July and September, 2006. During the study pharmacists reviewed 2,690 e-prescription orders (new = 83.0%, refill =17.0%) and intervened 102 times for an intervention rate of 3.8%. The rate at which pharmacists identified problems on new e-Rxs was found to be nearly twice that of refills (4.1% and 2.2%, respectively). The most common reason for pharmacists' interventions on e-prescriptions was to supplement omitted information (31.9%), especially missing directions. Dosing errors were also quite common (17.7%). The most common response by pharmacists to e-Rx problems was to contact the prescriber (64.1%), consult the patient's profile or medication history (12.8%), and/or interview the patient or the patient's representative (9.4%). In most cases (56%), the e-Rx order was changed and the prescription was ultimately dispensed. In 15% of cases the e-Rx order was dispensed as written following clarification by the prescriber. In 10% of cases the prescription was not dispensed. An additional 12% of prescription issues remained unresolved. Pharmacists required an average of 6.07 minutes to conduct their interventions on problematic e-prescription orders, representing an incremental dispensing cost of $4.74. CONCLUSION: Electronic prescribing has the potential to improve the safety and efficiency of patient care. However, as currently implemented in the community practice setting, it maintains selected threats to both. Best practice recommendations are offered to improve the implementation of this important technology.