Background Real-world data on BRAF-mutant non-small cell lung cancer (NSCLC) remain limited, particularly regarding outcomes with dabrafenib plus trametinib ( D + T ). Methods This multicenter retrospective study included 88 patients with advanced BRAF-mutant NSCLC treated across 30 centers. Clinicopathologic characteristics, treatment outcomes, and safety data were collected and analyzed. Patients received either chemotherapy or dabrafenib plus trametinib in the first-line or subsequent settings. Progression-free survival (PFS), overall survival (OS), and objective response rates (ORR) were compared across treatment groups. Results Among 88 patients (78 V600E, 10 non-V600E), median age was 64 years. Co-mutations were more frequent in non-V600E cases (40% vs. 10%). Brain metastases were more frequent in non-V600E cases (60% vs. 15%, p = .001). First-line D + T was associated with superior ORR (67% vs. 39%, p = .02), DCR (81% vs. 51%, p = .009), and PFS (median 13.1 vs. 6.1 months, p = .007) compared to chemotherapy, while OS was similar between groups. Among chemotherapy regimens, platinum-pemetrexed outperformed platinum-taxane in terms of ORR (77% vs. 33%, p = .006) and PFS (median 14.7 vs. 3.2 months, p = .002). No significant differences in efficacy were observed between first-line and later-line use of D + T . Co-mutations were associated with shorter OS (median 8.7 vs. 20.2 months, p = .009). PD-L1 status and BRAF subtype did not impact OS. Median treatment duration with D + T was 10.6 months, with treatment-related adverse events occurring in 61% of patients, most commonly fatigue and pyrexia. Conclusions In this real-world cohort, dabrafenib plus trametinib was associated with superior response rates and PFS compared to chemotherapy in the first-line setting. Presence of co-mutations was associated with poorer outcomes.