e21700 Background: Immune checkpoint inhibitors of programmed cell death-1 (PD-1) and its ligand (PD-L1) have been new standard of care for non-small cell cancer patients. However, little is known about the difference in efficacy between these two types of drugs. In this study, we aimed to assess the differences between anti-PD-1 and anti-PD-L1 in NSCLC treatment through a systematic review and meta-analysis. Methods: We systematically searched PubMed, CENTRAL, and Embase from January, 2000 to November, 2019. We also reviewed abstracts and presentations from all major conference proceedings. All randomized controlled trials that compared anti-PD-1/anti-PD-L1 with standard treatment in NSCLC cancer patients were selected as candidates. Studies with anti-PD-1 and anti-PD-L1 were screened and paired upon the mirror principle. The primary outcome was the difference in overall survival (OS). As the main results, indirect comparison of anti-PD-1 and anti-PD-L1 were calculated for each mirror group and then pooled using a random-effects model. Results: 16 randomized controlled trials were included for the meta-analysis. Overall, anti-PD-1 exhibited superior OS (HR 0.80, 95% CI 0.68-0.95, P= .01) over anti-PD-L1. Subgroup analysis showed that anti-PD-1 exhibited superior OS over anti-PD-L1 ICIs in combination therapy (HR 0.67, 95% CI 0.54-0.82, P <.01), but not in monotherapy (HR 0.89, 95% CI 0.74-1.06), 2nd line therapy (HR 0.84, 95% CI 0.66-1.06) or 1st line therapy (HR 0.77, 95% CI 0.58-1.03). Conclusions: The results demonstrated that anti-PD-1 exhibited favorable survival outcomes compared to anti-PD-L1 in NSCLC treatment, which provides an important guide for clinicians.