Background: Prospective data to guide management of elderly patients with metastatic colorectal cancer (mCRC) is limited. Whether elderly patients derive the same degree of benefit from doublet chemotherapy as younger patients is not well understood. In this study we utilized real-world data from patients in the United States (US) to evaluate treatment trends and compare overall survival (OS) in younger versus older patients with mCRC who receive first-line (1L) chemotherapy. Methods: The nationwide Flatiron Health electronic health record-derived de-identified database was used to select patients ≥50 years old (yo) with mCRC treated with 1L fluoropyrimidine-based chemotherapy with or without the addition of targeted therapy. Overall survival from the initiation of 1L therapy, stratified by receipt of a doublet or single agent cytotoxic chemotherapy regimen was assessed independently within three age cohorts (50-69; 70-74, ≥75) using both a cox proportional hazard model and a propensity score weighted analysis to control for potential confounding variables. A subgroup analysis was performed in patients receiving bevacizumab as part of 1L therapy. Results: Of 14,440 patients who received 1L chemotherapy, 5,874 (40.7%) were ≥70 yo, including 3,656 (25.4%) who were 75 or older. Doublet chemotherapy was received by 7,505 (87.6%) patients age 50-64 yo, 1892 (85.3%) patients age 70-74 yo, and 2297 (62.2%) patients age 75 and above. In all three groups, multivariate analysis of single agent chemotherapy vs doublet chemotherapy showed a benefit to doublet chemotherapy with a hazard ratio of 1.14, (95% CI 1.04-1.24, p = 0.006), 1.22 (95% CI 1.05-1.42, p = 0.011) and 1.19 (95% CI 1.10-1.29, p < 0.001), respectively. Similar results were noted when comparing doublet to single agent chemotherapy in the age 70-74 and ≥75 groups using a propensity score weighted analysis. In the subgroup of patients age ≥70 who received 1L bevacizumab, 2,604 received doublet chemotherapy and 441 received single agent chemotherapy. Median OS was 19 mos (95% CI: 18-20) vs 13 (95% CI: 11-15) vs with a propensity score weighted HR of 1.35 (95% CI 1.12-1.63, p = 0.001). Conclusions: A smaller percentage of patients over age 75 receive 1L doublet chemotherapy for mCRC in the US compared to patients age 50-69 or 70-74. Regardless of age, patients who receive doublet fluoropyrimidine-based chemotherapy appear to have improved overall survival compared to single agent chemotherapy. This retrospective US data is in contrast with recently presented data from a prospective phase III trial in Japan (JCOG1018). Elderly patients in the US should not be excluded from receiving doublet chemotherapy for mCRC without further prospective data.