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Abstract Introduction Chemical ablation with acetic acid or ethanol is effective against hepatocellular carcinoma and therefore its application in peripheral non-small-cell lung cancer (NSCLC) may be beneficial. Aim The aim of the study was to assess the efficacy and safety of percutaneous chemical ablation using acetic acid or ethanol in peripheral NSCLC cases. Patients and methods This was a prospective randomized control study conducted at the Chest and Clinical Oncology Departments, Mansoura, Egypt, from 2011 to 2014. Thirty-three patients were included with a mean age of 60 years, and were randomly divided into three groups: group A (acetic acid plus chemotherapy group) consisted of nine patients; group B (ethanol plus chemotherapy group) consisted of nine patients; and the control group C (chemotherapy alone group) consisted of 15 patients. Patients who were operable, who had tumors infiltrating the main stem bronchi or mediastinum, and those who refused to complete the study were excluded. Clinical and radiological data were evaluated before treatment and 3 and 6 months after treatment. Results There was a significant reduction in both cough score and chest pain in group A after 6 months of treatment, in the hemoptysis score in group A and group B after 6 months of treatment, and in dyspnea score in groups A and B after 3 and 6 months of treatment. There was a statistically significant difference in the tumor response results in both groups after 3 and 6 months of treatment when compared with the control group. There were one or more immediate complications but all were controllable with no mortality. Survival was better in groups A and B than in the control group. The cost of acetic acid and ethanol palliation for each patient was 10 $US. Conclusion Chemical ablation is an effective and inexpensive adjuvant palliative treatment for patients with inoperable peripheral NSCLC.