Squamous cell carcinoma of the buccal mucosa is a common cancer in India. We are referred a large number of locally advanced lesions where curative surgery is still possible. The objective of this study is to determine the role of post-operative radiotherapy in enhancing disease-free survival. Patients with stages III and IV cancer of the buccal mucosa potentially curable by surgery were randomized to surgery only or post-operative radiotherapy. Patients were followed up for 3 years. The clinico-pathological features in both arms were comparable. Disease-free survival at the end of the study was found to be 38% and 68% (P<0.005) respectively. Post-operative radiotherapy was thus seen to improve disease-free survival in squamous cell carcinoma of the buccal mucosa.