OBJECTIVES: Pemetrexed (Pem) was recently approved in the US for maintenance treatment of patients with advanced nonsquamous non-small cell lung cancer (NSCLC) whose disease has not progressed after 4 cycles of platinum-based first-line chemotherapy. The objective of this study was to estimate the budgetary impact of adopting Pem in this new indication from a US health plan’s perspective. METHODS: A deterministic model was developed from the perspective of a one-million member health plan. A survey of 300 oncologists was used to estimate the market shares of maintenance therapies before and after introducing Pem. Drug costs were obtained from Medicare reimbursement rates; non-drug costs from a claims database analysis. The number of maintenance-eligible patients was calculated from SEER incidence rates and the estimated proportions of NSCLC patients beginning and completing platinum-based first-line chemotherapy with stable disease or better. Model outputs included annual health plan cost, and costs per member per month (PMPM) and per treated member per month (PTMPM). One-way sensitivity analyses assessed the effect of changing input values. RESULTS: Assuming a 50% increase in the number of patients receiving maintenance therapy from 26 to 39 in a one-million member health plan, the model estimates a total annual cost increase of $365,323. Savings from patients who would have continued first-line therapy at an annual cost of $48,253 result in an estimated net budget impact of $317,070 translating into a PTMPM of $679.22 and PMPM of $0.026. The PMPM is sensitive only to the expected increase in maintenance use. CONCLUSIONS: The adoption of Pem as maintenance therapy is anticipated to increase the number of patients receiving maintenance treatment while reducing the number of patients continuing first-line therapy. This increase in maintenance therapy utilization is expected to increase the budget impact for a health plan by less than $0.03 per member per month.