Objectives: To present a methodology for identifying specific medications for which pill splitting is clinically appropriate and cost saving, to present data from a commercial managed care population on current pill-splitting practices, and to estimate additional cost savings from extended use of this strategy., Study Design: Retrospective pharmacy claims analysis., Methods: Pharmacy claims data from a commercial managed care health plan covering 19,000 lives and national drug data were used to compile a list of frequently prescribed medications. Excluding medications in which packaging, formulation, and potential adverse pharmacologic outcomes prohibited splitting, we performed a cost analysis of medications amenable to splitting., Results: Eleven medications amenable to pill splitting were identified based on potential cost savings and clinical appropriateness: clonazepam, doxazosin, atorvastatin, pravastatin, citalopram, sertraline, paroxetine, lisinopril, nefazadone, olanzapine, and sildenafil. For these medications, pill splitting is currently infrequent, accounting for annual savings of $6200 (or $0.03 per member per month), just 2% of the potential $259,500 (or $1.14 per member per month) that more comprehensive pill-splitting practices could save annually., Conclusions: Pill splitting can be a cost-saving practice when implemented judiciously using drug- and patient-specific criteria aimed at clinical safety, although this strategy is used infrequently.