Background: In non-small cell lung cancers with a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) of ≥50%, first-line treatment with the PD-1 inhibitor pembrolizumab improves survival compared to platinum-doublet chemotherapy. Whether higher PD-L1 expression levels within the TPS range of 50-100% predict for even greater benefit to pembrolizumab is currently unknown. Methods: In this multicenter retrospective analysis, we analyzed the impact of PD-L1 expression levels on the overall response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) in patients who received commercial pembrolizumab as first-line treatment for advanced NSCLC with a PD-L1 TPS of ≥50%. Results: Among 196 patients with NSCLC treated with first-line pembrolizumab, the ORR was 43.8% (95%CI: 36.8-51.1). At a median follow-up of 12.6 months (95%CI: 11.6-13.7), the mPFS was 6.2 months (95% CI: 4.2-8.2) and the mOS was not reached. The median PD-L1 TPS among patients who experienced a response to pembrolizumab was significantly higher than in patients with stable or progressive disease (TPS 90% vs 70%, P < 0.001), so a TPS cut point of 90% was chosen for further analysis. Baseline clinicopathological characteristics were well-balanced between patients with a PD-L1 TPS of 50-89% vs 90-100%. Compared to patients with a PD-L1 TPS of 50-89% (N = 114, 58.2% of the cohort), patients with a TPS of 90-100% (N = 82, 41.8% of the cohort) had a significantly higher ORR (61.0% versus 31.6%, P < 0.001), a significantly longer mPFS (13.2 versus 3.7 months, HR: 0.48 [95% CI: 0.33-0.71], P < 0.001), and a significantly longer mOS (NR versus 16.0 months, HR: 0.38 [95% CI: 0.21-0.70], P = 0.002). After adjusting for ECOG performance status and smoking history, PD-L1 TPS of 90-100% was significantly associated with improved mPFS (HR: 0.51 [95% CI: 0.34-0.75], P < 0.001) and mOS (HR: 0.38 [95% CI: 0.21-0.70], P = 0.001). Conclusions: Among patients with NSCLC and a PD-L1 TPS ≥50%, clinical outcomes are improved in the subgroup of patients with a PD-L1 TPS of ≥90%. These findings have implications for treatment selection as well as for clinical trial interpretation and design.