Background: For non-small cell lung cancer (NSCLC) patients on antithrombotic therapy who are treated with microwave ablation (MWA), the transient interruption of antithrombotic agents may increase the risk of thromboembolism, and continuation of antithrombotic agents may increase the risk of intraprocedural hemorrhage. This retrospective cohort study aimed to explore the safety of MWA in patients with NSCLC on antithrombotic therapy.Methods: A total of 572 patients with NSCLC (antithrombotic therapy group: n=84, Group A; control group: n=488, Group B) who received MWA were included. Antithrombotic agent use was suspended before MWA and resumed as soon as possible after MWA. Hemorrhagic (hemothorax and hemoptysis) and thromboembolic complications (pulmonary embolism, cerebral infarction, and angina) were compared.Logistic regression analyses were used to investigate the predictors of hemorrhagic complications after MWA.Results: Hemorrhagic complications occurred in 8 participants (9.5%) from Group A and 33 participants (6.8%) from Group B, and no statistically significant difference was found (P=0.365). There were 3 participants (0.5%) who developed thromboembolic complications, including 1 case (1.2%, 1/84) of pulmonary embolism in Group A, and 2 cases (0.4%, 2/488) of cerebral infarction or angina in Group B; no significant difference was found (P=0.923). In the subgroup analyses of Group A, no statistically significant difference of hemorrhagic (P>0.999) or thromboembolic complications (P>0.999) was found between patients who received and did not receive bridging anticoagulation with heparin. Logistic regression analyses revealed that direct contact of a tumor with vessels ≥2 mm was a predictor of hemorrhagic complications [hazard ratio (HR) =2.318; 95% confidence interval (CI): 1.215-4.420; P=0.011], while antithrombotic therapy was irrelevant.Conclusions: With the appropriate cessation and resumption of antithrombotic agents, patients with NSCLC on antithrombotic therapy have comparable incidence rates of hemorrhagic and thromboembolic complications after MWA to those of patients who are not on antithrombotic therapy. Therefore, with appropriate cessation, MWA appears to generally be safe for NSCLC patients on antithrombotic therapy.