OBJECTIVES: MTM services aim to optimize care and reduce costs for patients taking multiple chronic drugs (poly-pharmacy). This study examined the impact of face-to-face MTM services on drug expenditures, medical expenditures and total health care costs in. METHODS: MarketScan Commercial Claims and Encounters database was used to select: adults >18 years between January 1, 2007 and December 31, 2010, with face-to-face MTM (CPT codes 99605, 99606, 99607), and poly-pharmacy (4 or more chronic medications in the 6-months prior to index date). The date of the first MTM encounter was the index date. A (100:1) age, gender-matched poly-pharmacy control group was formed; the index date was that of the matched MTM patient. Nearest-neighbor propensity score matching within a caliper (1:1) was run to form two exchangeable study groups (n=401) controlling for demographic, drug-related, clinical status- related and health services utilization-related covariates. A difference-in-differences (DID) model with gamma distribution and log link accounting for three times points (period 0: 6 months pre, periods 1 and 2: 6 and 12 months post index date respectively) was run for total costs and medical costs. RESULTS: Unadjusted DID estimates for period 1 were $3,327 and $6,496 for period 2. DID models showed that total health care costs were not significantly different between the two groups in period 1 but were 32% less (CI:7%-51%, p-value=0.017) in the MTM group in period 2. Period 2 cost reduction was driven by medical costs (34% reduction, CI:2%-44%, p-value=0.037); no significant differences in pharmacy costs were observed in both periods. CONCLUSIONS: Face-to-face MTM services reduced medical costs with no change in pharmacy costs for poly-pharmacy patients. Favorable economic outcomes were detected seven months after initial MTM exposure. MTM plays a crucial role in reducing overall health care costs for chronic poly-pharmacy patients.