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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. [ABSTRACT FROM AUTHOR]