Background: Until the global approval of pembrolizumab for the treatment of first line (1L) MSI-H/dMMR metastatic CRC (mCRC), newly diagnosed patients were managed with standard of care (SOC) treatments like chemotherapy with or without an EGFR/VEGF inhibitor, independent of biomarker testing or status. This study assessed the RW SOC treatment patterns and outcomes among 1L MSI-H/dMMR mCRC patients. Methods: A retrospective observational study was conducted among patients ≥18 years diagnosed with stage IV MSI-H/dMMR mCRC (index event) who received care in the US community-based Oncology Network. Eligible patients were identified between 01-Jun-2017 to 29-Feb-2020 and followed longitudinally until 31-Aug-2020, last patient record, or date of death: whichever occurred first. Baseline demographics, clinical characteristics, treatment patterns and clinical outcomes were reported descriptively. Key clinical outcomes of interest were time to treatment discontinuation (TTD), rw-progression free survival (rwPFS) and overall survival (OS). Kaplan-Meier survival analysis was conducted for all time-to-event variables. Results: 150 MSI-H/dMMR CRC patients treated in the 1L setting were included, of which 38.7% were treated with chemotherapy and 61.3% with chemotherapy + an EGFR/VEGF inhibitor. Nearly 75% of patients had an ECOG PS of 0-1, and the time from diagnosis of metastatic disease to initiation of 1L treatment was 5.2 (0.1, 1157.4) weeks. The median duration of follow-up was 12.9 (0.1, 37.1) and 16.2 (0.8, 36.2) months among patients treated with chemotherapy and chemotherapy + EGFR/VEGF inhibitors, respectively. Within the chemotherapy group, 86% received FOLFOX while 14% received FOLFIRI. Within the chemotherapy + EGFR/VEGF group, the most common regimen was FOLFOX+bevacizumab (67%). Conclusions: The totality of RW clinical outcomes in 1L MSI-h/dMMR mCRC suggest that despite the availability of chemotherapy and EGFR/VEGF inhibitors, an unmet need still exists that may be addressed with the recent availability of pembrolizumab for select patients. This data further supports the rationale for biomarker testing and personalized treatment of 1L CRC. Patient characteristics and clinical outcomes are summarized in the table.