Background: Constituting up to 85% of all lung cancer, non-small cell lung cancer (NSCLC) is unfortunately often discovered in the metastatic setting. Profiling tumors for driver mutations and assessing PD-L1 expression have become essential in tailoring treatment. National guidelines recommend that patients with PD-L1 expression ≥ 50% may receive immunotherapy (IO) alone or chemotherapy in conjunction with immunotherapy (ChT/IO). At present, there is no strong data suggesting that the addition of chemotherapy to IO is superior to IO alone in this patient subgroup, and treatment decision is entirely physician dependent. This decision is often based on factors such as age, performance status, co-morbidities and disease burden with elderly/frail patients receiving IO alone compared to the younger population with higher disease burden receiving the combination. The aim of our study was to evaluate whether there is a difference in survival outcomes for patients with high PD-L1 expression receiving combination ChT/IO versus IO alone. Methods: We performed a retrospective analysis on stage IV NSCLC patients treated with either ChT plus pembrolizumab or pembrolizumab monotherapy in the first line setting from December 2016 to December 2019. PD-L1 status was evaluated for all patients and only patients with PD-L1 expression ≥ 50% were included in the analysis. Univariable and multivariable analyses identified characteristics predictive of overall survival (OS) and progression-free survival (PFS). OS was calculated using Kaplan Meier curves to present the cumulative probability of survival, and log-rank statistics were used to assess statistical significance between groups. Results: 195 patients were evaluated out of which 82 (42%) patients were identified as having PD-L1 expression ≥ 50%. 13 (13.4%) out of 82 patients received chemotherapy alone and were therefore excluded from the analysis. 49 (71%) patients received IO alone compared to 20 (29%) who received combination ChT/IO. Median PFS was 8.1 months (IO alone group) vs 9.9 months (ChT/IO group) with a hazard ratio (HR) of 0.95 (95% confidence interval [CI] 0.54-1.7, p = 0.87). Median OS was 13.7 months (IO alone group) vs 19 months (ChT/IO group) with a HR of 0.76 (95% [CI] 0.41-1.4, p = 0.42). Our results did not show a statistically significant difference between patients treated with IO alone vs combination ChT/IO. Conclusions: Our retrospective analysis revealed that although there was no statistically significant difference between high PD-L1 NSCLC patients receiving ChT/IO vs IO alone with respect to survival, there was a trend towards improved PFS and particularly OS in favor of the group receiving chemotherapy in combination with immunotherapy. Given our small sample size, further studies are needed to determine the benefit of adding chemotherapy to IO for NSCLC patients with high PD-L1 expression.