OBJECTIVES: While high-dose dexamethasone (Dex; 480 mg/cycle) is effective in combination with lenalidomide (Len) in relapsed/refractory multiple myeloma (RRMM) patients, emerging evidence points to increased use of low-dose (≤160 mg/cycle) Dex in this combination regimen. We assessed frequency of use of high- vs low-dose Dex in RRMM patients in real-world practice in the US. METHODS: Patients who received treatment for myeloma between July 2012–September 2014 were identified from a large US claims database. Index date was defined as the first diagnosis of multiple myeloma or claim for a myeloma drug during the study period. Patients were stratified into two groups: Group (G)1 if they had continuous enrollment and prescription eligibility for a 12-month period prior to index date (indicating newly diagnosed, treatment-naïve status); G2 if they did not have 12-month continuous enrollment prior to index date. Dex dose per cycle in the first four cycles of Len-Dex treatment in RRMM patients was evaluated. RESULTS: Overall, 8891 and 16,489 patients were identified in G1 and G2, respectively. In total, 6620 distinct lines of treatment (LOTs) were identified in G1 and 29,287 in G2. Len-Dex RRMM LOTs accounted for 4.6% (n=304) in G1 and 7.1% (n=2080) in G2. The median (Q1–Q3) Dex dose per cycle across the first four cycles in RRMM LOTs was 121 (75–156) mg in G1 and 102 (70–154) mg in G2. In G1, median dose was consistent across LOTs 2, 3 and 4 (137, 113 and 114 mg/cycle, respectively). More than two-thirds of these LOTs showed a Dex dose of ≤160 mg/cycle. CONCLUSIONS: This real-world study of Len-Dex use among RRMM patients shows that the majority receive low-dose Dex, and confirms the growing use of low-dose Dex in this combination regimen. Additional analyses may inform revision of treatment guidelines for RRMM.