OBJECTIVES: Tablet splitting is utilized as a method of avoiding high costs associated with drug therapy. Our healthcare system encourages tablet splitting of approved medications by patients who are willing and physically able. An analysis was performed to project annual cost savings following electronic implementation of an approved tablet splitting guide. METHODS: A tablet splitting guide was developed to identify appropriate high cost medications for tablet splitting. Tablets with narrow therapeutic range, formulations potentially compromised by splitting, and those difficult to split consistently were excluded from the guide. Providers in our healthcare system enter all medication orders electronically through a computerized patient record system. The database was programmed to default to tablet splitting for the medications and dosages specified in the guide when selected by the provider. For example, if simvastatin 40mg dose were selected, the computer would automatically select the 80mg tablet and incorporate patient instructions to take one-half tablet. Staff was notified of the programming change prior to execution, to ensure proper counselling of patients. It was assumed that the rate of tablet splitting would have remained unchanged without the electronic implementation. Therefore, cost savings for each medication and dose was calculated by multiplying the absolute number of prescriptions by the percent increase in tablet splitting realized. Difference in cost per year between utilizing whole and half tablets was applied to the additional number of prescriptions tablet split. RESULTS: Analysis was performed on selected prescription data including rosiglitazone, atorvastatin, simvastatin, sertraline, paroxetine, risperidone, and olanzapine. Prior to implementation, only 65% (3918/6000) of eligible prescriptions were tablet split. Within six months, the rate increased to 80% (5357/6680) with an estimated annual cost savings of US$158,000.00. Rate increased 10-92% per medication. CONCLUSIONS: Incorporating a tablet splitting guide with physician order entry is an efficient method of realizing substantial cost savings.