Background: MM is the second most common hematologic malignancy in adults. Few studies have evaluated the economic impact associated with MM treatment. Methods: This retrospective study identified patients (pts) aged ≥ 18 yrs with ≥ 2 claims for MM (ICD-9 203.00) and ≥ 1 claim for anti-cancer systemic therapy (A-CST) in a large national US claims database between Jan 2008 and Aug 2013; first MM claim date was the index date. Pts required continuous enrollment (CE) in the health plan for 6 mos pre- and ≥ 6 mos post-index date ( < 6 mos if due to death), and no evidence of any cancers or A-CST in the pre-index period. Treatment patterns, HRU (inpatient, office, outpatient, and ER visits), and costs (drug and medical costs) during LOT1 were examined. LOT1 started with first A-CST; regimens included all agents received in the first 30 d. LOT1 ended at the earliest of: start of a new drug, ≥ 60-d gap after run-out of initial regimen drugs, death, or end of CE/study period (these censored LOTs were included). Results: Of 2053 pts, median age was 67 yrs (42% ≥ 70 yrs), 55% were male, and 638 (31%) had hematopoietic cell transplant (HCT) after LOT1 start. Median length of LOT1 was 4.3 mos (mean 6 mos). During LOT1, 96%, 90%, 43%, and 38% pts had ≥ 1 office, hospital outpatient, ER visit, and inpatient stay, respectively. Most common regimens were bortezomib ± dexamethasone (V±d, 25%), lenalidomide ±d (R±d, 17%), and VR±d (14%); in HCT pts, most common regimens were VR±d (25%), V±d (25%), and R±d (16%). Unadjusted per-pt per-month (PPPM) costs in HCT pts were $24,290 (SD $16,619; range $16,401–30,929 depending on initial regimen) and in non-HCT pts were $14,610 (SD $24,875; range $10,214–24,492). Drug and administration costs accounted for 37% of LOT1 costs and varied by initial regimen. 1-year costs after LOT1 initiation were $171,513 (SD $142,511; range $97,076–259,531). Adjusted (by initial regimen, pt characteristics, HCT, and baseline comorbidities) LOT1 costs were not significantly different with V±d and R±d; VR±d costs were higher vs V±d. Conclusions: HRU and costs were high during LOT1. Overall healthcare costs for LOT1 ranged from $10,214 to $30,909 PPPM depending on initial regimen and receipt of HCT.