Background: Pembrolizumab (Pembro) is used in first-line treatment of patients with metastatic non-squamous non-small cell lung cancer (NSQ NSCLC) as monotherapy and in combination with pemetrexed and platinum agent (Pembro+Pem+Plat). Pembro monotherapy is approved for patients whose tumors express PD-L1 Tumor Proportion Score (TPS) ≥ 1% while triplet therapy is approved regardless of PD-L1 TPS. These 2 regimens have not been compared in a head-to-head trial, and real world (RW) treatment pattern data are lacking. This study used RW data to describe patients who received Pembro or Pembro+Pem+Plat and associated overall survival (OS). Methods: This retrospective observational study selected adult patients with diagnosis of advanced NSQ NSCLC who started first-line treatment with Pembro or Pembro+Pem+Plat between Mar. 2015- Aug. 2018 in Flatiron Health’s electronic health record-derived database. Patient characteristics were summarized descriptively, and the Kaplan-Meier survival method was used (unadjusted). Results: A total of 1137 patients received Pembro (median age 72 years) and 1068 patients received Pembro+Pem+Plat (median age 67 years). Patient characteristics are shown in the Table. Median OS was 11.9 months for the Pembro cohort and 14.3 months for the Pembro+Pem+Plat cohort. Median OS by PD-L1 TPS was TPS < 1%: 8.8 months for Pembro and 9.5 months for Pembro+Pem+Plat, TPS 1-49%: 8.9 months for Pembro and not reached (NR) for Pembro+Pem+Plat, and TPS ≥50%: 13.4 months for Pembro and NR for Pembro+Pem+Plat. Conclusions: These RW data seem to suggest baseline differences between the population with Pembro and Pembro+Pem+Plat with regard to age, PS, disease stage, as well as PD-L1 status. Those baseline differences may play a role in the clinicians’ choice of the two treatment options for the NSCLC patients.