Background: Lung cancer is the leading cause of cancer-related death in the United States. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of non-small-cell lung cancer (NSCLC). Denosumab is a humanized monoclonal antibody to RANK ligand used to prevent skeletal-related events of bone metastases in solid tumors. In preclinical and some clinical studies, denosumab have shown to have some anti-tumor properties. We are reporting the clinical outcomes in our NSCLC patients who received RANKL inhibitor in combination with ICIs. Methods: This observational study used retrospective data from a tertiary cancer center from 2015-2020. Stage IV non-small cell lung cancer patients who received denosumab within 30 days of ICIs (pembrolizumab, nivolumab, atezolizumab, ipilimumab) were included. Median overall survival (OS), progression free survival (PFS), best radiographic responses were obtained. Univariate, multivariate analyses and logistic regression analyses were done, and Kaplan-Meier curves were obtained for survival analysis. Results: We identified 69 patients and all had skeletal metastasis, and 37.7% had brain metastases. Median duration of concomitant use of denosumab and ICI was 1.5 months. Median OS was 6.3 months and median PFS was 2.8 months. Overall response rate was 18.8% and disease control rate was 40.6%. Median OS in patients with concomitant denosumab and ICIs more than 3 months was 11.5 months, comparing to 3.6 months in patients with < 3 months of concomitant therapy (P=0.0005). OS and PFS did not differ with respect to brain metastases or number of skeletal metastases. However, the duration of ICIs and denosumab overlap was associated with improved OS and PFS. Among the 18.8% of patients who achieved complete response (CR) and partial response (PR), six-month survival rate was 100% and one-year survival rate was 69.2%. Conclusions: Patients receiving combination therapy did not perform poorly despite of poor prognostic features such as brain metastases and numerous skeletal metastases. Although we did notice potential benefit of the longer duration of concomitant use of ICI and denosumab, future prospective clinical trials are needed to evaluate the synergistic effect of RANKL inhibitors/ICI and if duration of RANKL inhibitors matters.