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Background: The aim of the study was to explore the outcomes of computed tomography-guided microwave ablation (MWA) in non-small cell lung cancer (NSCLC) patients with adjacent lobe invasion (ALI), and to compare the outcomes of ALI-NSCLC and non-ALI NSCLC patients after MWA., Methods: A total of 319 NSCLC patients and 366 tumors treated with MWA were included in the study, comprising 34 ALI-NSCLC patients and 285 non-ALI NSCLC patients. Complications, local recurrence rates, progression-free survival (PFS), and overall survival (OS) were compared. Logistic regression analyses were used to investigate the correlation between ALI and the occurrence of pneumothorax after MWA., Results: The mean tumor diameter of ablated tumors was 3.6 ± 2.2 cm. There were 95 (29.8%) NSCLC patients in which pneumothorax occurred after MWA, and all patients recovered. Of these, the ALI group had a significantly higher incidence rate of pneumothorax than the non-ALI group (52.9% vs. 27.0%, p = 0.002). The median PFS and OS for the ALI group were 12.0 ± 10.2 and 15.5 ± 9.5 months, respectively, and that of the non-ALI group were 13.0 ± 10.6 and 17.0 ± 11.1 months, respectively, and no significant difference was found in PFS (p = 0.329) nor OS (p = 0.394) between the two groups. Local recurrence rates for ALI and non-ALI groups were 29.4% and 20.7%, respectively, and no significant difference was found (p = 0.244). Logistic regression analyses revealed that ALI can increase the risk of pneumothorax (hazard ratio [HR], 2.867; p = 0.012)., Conclusions: MWA is an effective and safe approach for ALI-NSCLC treatment. Although ALI can increase the risk of pneumothorax, ALI-NSCLC patients reveal a comparable outcome to non-ALI NSCLC patients after MWA., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)