7054 Background: Lenalidomide (LEN) is approved for patients with lower-risk MDS with del5q who are transfusion-dependent (TD). We aimed to assess the prevalence and complications associated with LEN use in non-TD older patients with MDS. Methods: Using the SEER-Medicare database we identified Medicare enrollees diagnosed with MDS from 2007-2011. Medicare part D claims were analyzed for evidence of LEN use. CPT, HCPCS, and ICD-9 codes were used to characterize TD MDS (claims for ≥ 2 RBC transfusions within 8 weeks prior to LEN), complications, and baseline risk per SEER-Medicare MDS Risk Score (SMMRS; Uno, Leuk Res 2014). Incident complications during LEN were noted if there were no prior claims for the same within a 1-yr look-back window. Results: Among 469 patients initiating LEN (median age 78 years), 77% received it first-line, and 23% after a hypomethylating agent. Among all, 19% had del5q, 37% had non-del5q MDS, and 44% no histology specified (MDS NOS). SMMRS risk was evenly distributed between low (36%), intermediate (30%), and high (34%). Only 42% of patients were TD at the time of first LEN prescription, and 26% had not been transfused within six months prior to LEN. Non-TD patients receiving LEN were more likely to have lower-risk disease (p = .004), and less likely to have pre-treatment thrombocytopenia (p = .005) or neutropenia (p = .003); they did not differ significantly in age (p = .85), documentation of del5q (p = .51), comorbidity (p = .65) or treatment center volume (p = .80). Median days on LEN for the non-TD was 121. Incident complications post-LEN among the non-TD are shown. Conclusions:These data suggest there is widespread off-label use of LEN in older patients with MDS, as many receive the drug who are not TD. Moreover, off-label exposure to LEN in these patients is associated with a sizable risk of incident complications, which is difficult to justify given they are already living free of transfusion dependence. [Table: see text]