Background: Among patients with NSCLC and a PD-L1 TPS ≥50%, the response rate to the PD-1 inhibitor pembrolizumab is ~45%. Whether certain subsets of patients with a PD-L1 TPS ≥50% are more likely to benefit from treatment with a PD-1 inhibitor is currently unknown. We compared outcomes among NSCLC patients treated with first-line PD-1 inhibitors and different PD-L1 TPS groupings: 50-74% vs 75-100%. Methods: We retrospectively analyzed patients who received a PD-1 inhibitor as first-line treatment for NSCLC with a PD-L1 TPS of ≥50% from the Dana-Farber Cancer Institute and Memorial Sloan Kettering Cancer Center. Clinicopathologic characteristics and clinical outcomes were compared among patients with a PD-L1 TPS of 50-74% vs 75-100%. Event-time distributions were estimated using Kaplan-Meier and compared with the log-rank test. Results: 112 patients were identified for inclusion in this study: 39.3% (N = 44) had a PD-L1 TPS of 50-74%, and 60.7% (N = 68) had a TPS of 75-100%. There were no significant differences in smoking history, histology, sex, KRAS or EGFR mutation status, and age between both groups of patients. In the entire cohort, the overall response rate (ORR) was 33.9%, median progression-free survival (mPFS) was 4.2 months (95% CI: 2.8-6.2), median overall survival (mOS) was 20.3 months (95% CI: 17.7-NR). Patients with TPS 75-100% had a significantly higher ORR (13.6% vs 47.1%, P < 0.01), significantly longer mPFS (2.5 mo [95% CI: 1.8-4.5] vs 5.1 mo [95% CI: 3.8-7.4 ], P = 0.02), and higher estimated 12-month OS (76.4% vs 54.4%) compared to patients with TPS 50-74%. Conclusions: In the first-line setting for NSCLC, higher PD-L1 TPS levels of 75-100% is associated with improved clinical outcomes compared to patients with a TPS of 50-74%.