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Background Immunotherapy has shown survival benefit as both frontline and subsequent therapy in multiple cancers. However, its efficacy in patients with poor performance status is unknown since they are excluded from the clinical trials. We conducted a retrospective study to investigate the effect of poor performance status (PS) on survival in patients with non-small cell lung cancer (NSCLC) who received immunotherapy as a subsequent line of treatment. Methods We reviewed the medical records of 341 patients with NSCLC receiving immunotherapy as between July 2013 and June 2018. Progression-free survival and overall survival was calculated using Kaplan-Meier curve. Results The average age of patients was 66 years (range: 39–90 years), with a male predominance (57%). Majority of the patients were Caucasian (87%), followed by African-American (12%), and Asian (1%). Most of the patients were former smoker (72%), followed by current smoker (19%) and never smoker (7%). Adenocarcinoma and squamous cell carcinoma was diagnosed in 206 (60%) patients and 112 (33%) patients, respectively. The ECOG-PS was 0, 1, 2 and 3 in 46 (13%), 175 (51%), 86 (25%) and 34 (10%), respectively. Four different immunotherapies were used, namely atezolizumab in 10 (3%), durvalumab in 34 (10%), nivolumab in 152 (44%) and pembrolizumab in 144 (42%) patients. Average number of cycles of atezolizumab received by the patient was 6 (range 2–22 cycles), durvalumab 15 (range 1–29 cycles), nivolumab 11 (range 1–112 cycles), and pembrolizumab 12 (range 1–52 cycles). Patients were grouped in good performance status (ECOG 0–1) and poor performance status (ECOG ≥2). The median progression free survival (PFS) was 7 months (95% CI 6.3–8.2) in patients with good PS and 3 months (95% CI 1.8–4.6) in patients with poor performance status (p Conclusions Our data suggests that while the patients with poor PS tolerated the immunotherapy. However, poor PS was associated with significantly lower PFS and OS. Further studies are required to evaluate the effect of PS on survival in frontline immunotherapy. Acknowledgements We thank Dr. Saqib Abbasi for helpful discussions. Trial Registration N/A Ethics Approval The study was approved by the Institution Review Board at KUMC, #CR00009003. References N/A