The efficacy of immunotherapy for treatment of patients with oligometastatic non-small cell lung cancer (NSCLC) at different metastatic sites remains controversial. We investigated the effect of different metastatic sites on immunotherapy for oligometastatic NSCLC following local treatment (LT).We retrospectively analyzed patients with oligometastatic NSCLC from the latest 2018 registry on the SEER Stat software (8.3.9. Version) and a Chinese single-center cohort. The effects of immunotherapy on OS (overall survival) and CSS (cancer specific survival) were estimated for patients with different metastatic sites.A total of 483 patients in the SEER-18 database and 344 patients in the single-center cohort were included. Immunotherapy was significantly correlated with improved OS (SEER: Hazard ratio 0.754, 95% CI 0.609-0.932; P=0.044; China: Hazard ratio 0.697, 95% CI 0.542-0.896; P=0.005) and CSS (SEER: Hazard ratio 0.743, 95% CI 0.596-0.928; P=0.009; China: Hazard ratio 0.725, 95% CI 0.556-0.945; P=0.018). Subgroup analysis showed that OS was improved after immunotherapy in the BRM (SEER: Hazard ratio 0.565, 95% CI 0.385-0.829; P=0.004; China: Hazard ratio 0.536, 95% CI 0.312-0.920; P=0.024) and MOM (SEER: Hazard ratio 0.524, 95% CI 0.290-0.947; P=0.032; China: Hazard ratio 0.469, 95% CI 0.235-0.937; P=0.032) subgroups, but not in the BOM (SEER: P=0.334; China: P=0.441), LIM (SEER: P=0.301; China: P=0.357), or OTM (SEER: P=0.868; China: P=0.489) subgroups.This study showed that immunotherapy conferred survival benefits on patients with oligometastatic NSCLC. Our subgroup analysis suggested that patients with oligometastatic NSCLC in the brain or multiple organs may particularly benefit from aggressive front-line therapies.Copyright © 2022 Ma, Zhang, Wang, Yu and Chen.