e20087 Background: Image-guided thermal ablation (IGTA) is an effective treatment option for patients with non-small cell lung cancers (NSCLC), offering an excellent alternative to invasive surgery. We seek to compare long-term survival metrics between single and multifocal stage IA NSCLC patients who underwent IGTA. Methods: IRB-approved, HIPAA-compliant, retrospective study of patients who underwent IGTA for NSCLC during 2015 and 2016. Patient demographics, clinical and imaging follow-ups, tumor characteristics, and procedural technical outcomes were reviewed. We analyzed technical success, 5-year overall survival (OS), progression-free survival (PFS), cancer-specific survival (CSS), and Kaplan-Meier survival analysis between single and multifocal NSCLC cohorts, as well as different tumor stages. Results: 37 patients (mean ± SD age=71.6±8.8) ablated for single (n=15 (40.5%)) or multifocal (n=22 (59.5%)) NSCLC were identified. Multifocal NSCLC were sub-classified into 2-3 (n=12 (32.4%)) and ≥4 tumors (n=10 (27%)). All ablations were completed successfully. Across 119 IGTA encounters, patients were treated using cryoablation (n=66), microwave ablation (MWA) (n=49), and radiofrequency ablation (RFA) (n=4). At the time of ablation, individual nodules were staged at T1A=46 (38.7%), T1B=54 (45.4%), T1C=16 (13.5%) and T2A=3 (2.5%). Local recurrence was observed in 4/119 (3.3%) tumors; two were reablated once with MWA and cryoablation with no further recurrence, the third was reablated twice with MWA and had no recurrence, and the fourth was reablated once with MWA and subsequently treated with radiotherapy. Multifocal NSCLC patients exhibited significantly better 5-year OS of 85.6% compared to single NSCLC patients at 35.7% (HR=0.14, p=0.003, 95% CI: 0.037, 0.51). PFS and CSS at 5 years were higher for multifocal NSCLC compared to single NSCLC, but only significant for PFS (HR=0.25, p=0.014, 95% CI: 0.084, 0.76). PFS and CSS of subjects with ≥4 tumors were both 100%, 2-3 tumors at 58.7% and 90.9%, and single tumors at 35.7% and 83.1%, respectively. There was no significant difference between tumor T stages for OS and PFS (p=0.48 and p=0.56, respectively; see Table). No patient staged at T1A at the initial IGTA encounter died as a result of cancer, meaning cancer-specific survival was greatest in T1A tumors (see Table). Conclusions: IGTA is an effective treatment for multifocal and early-stage NSCLC. Our results demonstrated consistent trends in improved survival for multifocal NSCLC. The size of tumor up to 3 cm did not have significant impact on overall survival or progression-free survival. [Table: see text]