Background: Nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, disrupts PD-1-mediated signaling and may restore antitumor immunity in NSCLC patients. Methods: A retrospective review of data from 20 patient records were used to describe the response of patients with NSCLC receiving treatment with Nivolumab after failing chemotherapy. Two patients were too early to evaluate. Results: A total of 18 patients (pts) (10 males and 8 females) were included in the analysis. The median age was 66 years (range 46-85). Adenocarcinoma was documented in 15 pts and squamous cell carcinoma in 3 pts. A Ros-1 positive mutation was documented in 1 pt, 3 EGFR positive mutations were recorded and no pts tested positive for ALK. All pts failed frontline treatment: 14 pts failed platinum based chemotherapy and 4 pts failed TKI-inhibitors (3 on erlotinib and 1 on crizotinib). Pts received a median of 4 cycles of nivolumab (range 1-16). The performance status ranged from 0 to 2 (median 1). The median number of metastatic sites was 3 (range 1-5). Four partial responses were documented (23.5% 95% CI 3-43%), with response durations of 232, 113, 63 and 30 days. Disease stabilization was documented in 7 pts. There were no complete responses so far, and 6 pts showed progressive disease. Two pts were too early to evaluate and one pt was non-evaluable (died due to progresive diease before treatment initiation). No responses were seen amongst the pts who received prior TKI treatment. Documented toxicities included pulmonitis in 2 pts, chest infections in 4 pts (one pt with documented tuberculosis), fatigue in 4 pts and skin rash, diarrhoea and headaches in 1 pt, respectively. The median survival was 124 days (13-289). Conclusions: In this retrospective study nivolumab was an active and well tolerated treatment in pts with pretreated NSCLC.