OBJECTIVES: Rituximab based chemotherapy combinations are used to treat elderly patients with follicular lymphoma (FL), but the optimal regimen is unknown. We aimed to identify the cost-effectivness of first line rituximab-based combinations. METHODS:  Stage II-IV grade 1-3 FL patients >65 diagnosed between 2001-2010 who received chemotherapy within 6 months of diagnosis were identified using SEER. Healthcare costs from linked Medicare claims through 2014 were used to estimate costs using a phase of care approach and to calculate the incremental cost-effectiveness ratio (ICER). RESULTS:  Of the 2,827 pts, 587 received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP); 422 rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP); and 576 another rituximab combination (R-other). R-CHOP was more common in pts <75 (p<0.01), males (p=0.01), less comorbid (p<0.01), advanced stage disease (p=0.05), married (p<0.01), and those treated in a big metro area (p<0.01). Propensity weighting adjusted these differences prior to the analysis. Mean overall survival was 9.19 years for pts treated with R-CHOP, which was 0.19 years longer than R-CVP and 0.87 years longer than R-other. Total cost of care was $162,300 for R-CHOP, $141,000 for R-CVP, and $145,100 for R-other. The ICER for R-CHOP vs R-CVP was $19,800/LY, while for R-CHOP vs R-other $21,200/LY. For pts living longer than 2 years, mean monthly cost for the 1^styear after diagnosis was $1800, $1600, & $1600; and for the last year of life, $5900, $5700, & $4700 for R-CHOP, R-CVP, and R-other, respectively. CONCLUSIONS: In this first real world analysis comparing rituximab based combinations in older paients with FL, the addition of an anthracycline significantly prolongs overall survival after adjusting for baseline factors and is cost-effective. Additional research is needed to compare therapy after relapse as newer agents are expensive and likely contribute to the dramatic difference in cost between the first year after diagnosis and the last year of life.