In Brief OBJECTIVE To evaluate whether, and under what circumstances, trimonthly-cycle oral contraceptive pill (OCP) therapy is cost saving over standard-cycle OCP therapy for reducing the severity of menstrual-related symptoms. METHODS We created three economic models, with each model representing a unique cost perspective (societal, private third party, and patient), to estimate the incremental annual costs associated with women taking trimonthly-cycle rather than standard-cycle OCP. Direct costs considered were costs for OCP prescriptions, female hygiene products, generic over-the-counter pain relievers and iron tablets, home pregnancy tests, and physician visits for menstrual-related concerns. Indirect costs considered were lost wages due to menstruation-related disability and opportunity costs of physician visits. We derived base-case and sensitivity range estimates from prior literature, public use data, expert opinion, and cross-sectional survey data that we collected from 59 adult women taking standard-cycle OCP visiting a large, community-based gynecology office. All costs were adjusted to 2002 US dollars. RESULTS Under base-case assumptions that both regimens were equivalently priced ($1.16/pill) and trimonthly OCP reduces hygiene product use by 50%, annual societal costs per person were $460 for trimonthly OCP and $501 for standard OCP (incremental cost savings = $41). Assuming no difference in monthly drug copayment costs between the two regimens ($5.00), annual private third-party costs were nearly identical at $365 per regimen. Annual patient costs were $95 for trimonthly OCP and $136 for standard OCP. Trimonthly OCP remained cost saving to society as long its price remained below a 9% premium to standard OCP prices. The degree to which trimonthly OCP reduces hygiene product use also significantly influenced the cost difference between the two regimens. CONCLUSION Compared with standard-cycle OCP, tri-monthly-cycle OCP appears to be associated with significant societal and patient cost savings. These savings are highly conditional upon trimonthly OCP being priced similarly to standard OCP. Compared with standard-cycle oral contraceptive regimens, the trimonthly-cycle regimen holds considerable promise as a way to reduce direct and indirect costs associated with monthly menstruation.