Consolidation immunotherapy (IO) has transformed the therapeutic landscape for patients (pts) with locally advanced NSCLC. Its impact on health-related quality of life (HRQoL) has yet to be assessed outside the clinical trial context. The main objective of the OBSTINATE (GFPC 06-2019) study is to prospectively evaluate HRQoL in unresectable stage III NSCLC in « real-world » condition. OBSTINATE is a nationwide prospective multicentric study currently open for inclusion in France (NCT05049044). All pts diagnosed with unresectable stage III NSCLC and able to complete HRQoL self-assessed questionnaires (EORTC QLQ-C30, QLQ-LC13 and EQ-5D-5L) are eligible. HRQoL evaluation are prespecified according the treatment strategy for each patient included. Between 12/2020 and 11/2021, 162 pts were included in the study from 25 participating centers in France. The population was mainly male (70.8%), with smoking history (94.4%), good ECOG PS (0/1: 92.3%) and median age of 67 years (45-92). TNM stage was IIIA, IIIB and IIIC for 38.5%, 46.8% and 14.1% of pts respectively. Squamous cell carcinoma was the main pathological subtype (45.2%). PD-L1 status was known for 95% of pts (<1%: 11.2% ; 1-49%: 50.5%; ≥50%: 38.3%). Patients were clustered according planned therapeutic strategy at diagnosis: concomitant radio-chemotherapy (cRT-CT)+/-IO (n = 85, 52.2%); sequential (s)RT-CT+/-IO (n=27, 16.9%); CT+/-IO (n=41, 25.6%); exclusive RT (n=1, 0.6%); IO (n=5, 3.1%); others (n=2, 1.2%). At diagnosis, trend to higher HRQoL level in pts referred to cRT-CT+/-IO compared to sRT-CT+/-IO or CT+/-IO, notably for role (mean score of 76.5±26.0 vs 65.3±34.7), emotional (mean score of 77.2±22.7 vs 66.7±25.7) and cognitive functioning (mean score of 88.3±17.6 vs 78.0±22.6). Consistently, global health status and utility scores tends to be higher in the cRT-CT+/-IO group at diagnosis. OBSTINATE is the first study to prospectively evaluate HRQoL in unresectable stage III NSCLC on a national scale. At diagnosis, pts referred to concomitant RT-CT+/-IO treatment tend to show higher HRQoL. Further follow-up is needed to evaluate modification of HRQoL during treatment.