Background: Anti-PD-1 therapy with nivolumab has demonstrated improved overall survival (OS) in patients with non-small-cell-lung cancer (NSCLC). Indeed, since CheckMate 017 and 057 results, nivolumab is considered as the standard of care for second line treatment of recurrent/refractory NSCLC. In the setting of advanced/metastatic NSCLC, radiotherapy, whatever its modality, is routinely used, with curative or palliative intention. Many patients receive nivolumab and radiotherapy, concomitantly or not, during the course of their disease. A synergistic effect may occur. However data concerning this therapeutic association for NSCLC are rare. Pending the outcomes of prospective trials we report a large series of NSCLC patients who were treated with any radiotherapy and nivolumab in order to assess toxicity and efficacy. Methods: We retrospectively reviewed records from patients of three French centers, with metastatic or refractory NSCLC irradiated, concomitantly or from six months before to three months after nivolumab. Toxicities and outcomes were analysed. Results: We included 103 patients (144 cranial and extra-cranial irradiated targets). An adverse event (AE) was observed in 62 (60.2%) patients and grade 3-4 AE in 10% of patients. Among them, 9 patients reported 12 grade III-IV nivolumab related side effects,. Patients having received irradiation before nivolumab presented a higher risk of grade III-IV AE in comparison of with patients who received it during or after nivolumab (p = 0.001). One and 2years OS rates were 49.3% and 29.4% respectively whereas 1- and 2-years PFS were 18.8% and 10.2% respectively. Timing of irradiation delivery, before or after/during nivolumab administration was not associated to a better OS or PFS. Patients with nivolumab relative AE had statistically a better OS (p = 0.05) in comparison with patients without anti-PD1 toxicity. Conclusions: The combination of nivolumab with radiotherapy in patients with NSCLC was not associated with an increased risk of severe or unexpected toxicities. This study provides reassuring elements, to propose this association in clinical practice, when palliative irradiation is necessary.