Immune-checkpoint blockade in front-line or second-line treatment improves survival in advanced non-small cell lung cancer (aNSCLC) when compared with chemotherapy alone. However, easily applicable predictive parameters are necessary to guide immune-checkpoint inhibition in clinical practice. In this retrospective bi-centric analysis, we investigated the impact of baseline patient and tumor characteristics on clinical outcome in aNSCLC patients treated with programmed cell death protein 1(PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors. Between May 2015 and January 2018, 142 unselected consecutive NSCLC patients received PD-1/PD-L1 inhibitors during the course of disease. In multivariate analysis, we identified the Eastern Cooperative Oncology Group (ECOG) performance status (ECOG > / 1 versus ECOG &le / 1, HR: 3.23, 95%CI: 1.58&ndash / 6.60, P = 0.001), baseline absolute lymphocyte count (ALC / high: > / 0.93 × / 109/L versus low: &le / 0.93 × / 109/L, HR: 0.38, 95%CI: 0.23&ndash / 0.62, P < / 0.001), prior or concomitant anti-vascular endothelial growth factor (VEGF) targeting therapy (yes versus no, HR: 2.18, 95%CI: 1.15&ndash / 4.14, P = 0.017) and TNM stage (IV versus III, HR: 4.18, 95%CI: 1.01&ndash / 17.36, P = 0.049) as the most relevant parameters for survival. Neither antibiotic exposure (antibiotic-positive versus antibiotic-negative, HR: 0.90, 95%CI: 0.56&ndash / 1.45, P = 0.675), nor PD-L1 expression on tumor cells (&ge / 1% versus < / 1%, HR: 0.68, 95%CI: 0.41&ndash / 1.13, P = 0.140) was associated with survival. Baseline ECOG performance status and ALC were associated with survival in aNSCLC patients treated with PD-1/PD-L1 inhibitors and assessment of these parameters could be suitable in clinical practice.