It is well established that most invasive oral cancers arise from precancerous lesions such as leukoplakia, erythroplakia and oral submucous fibrosis. One of the approaches for control of oral cancer is to detect oral precancerous lesions early in their development and prevent their malignant transformation to invasive cancer either by chemoprevention or by surgical excision of the lesions, with concurrent control of tobacco and alcohol use and other specific aetiological factors. However, the value of specific approaches such surgery in long-term control of lesions and prevention of malignant transformation is not known. We describe our experience with cold knife surgical excision of 59 cases of non-homogeneous leukoplakia of the oral cavity diagnosed in the context of a community-based oral cancer cluster randomised oral cancer screening trial in Kerala, India. Two-thirds of these revealed dysplasia on histology. After a minimum follow-up of 12 months (range 12-37 months) after surgical excision, 44 (74.8%) were remaining disease free with no evidence of recurrent/new lesions; during follow-up, three (5%) developed new luekoplakic lesions, and six (10.1%) developed recurrent lesions, while six (10.1%) could not be traced after treatment. There was no event of malignant change during follow-up. The proportion of subjects remaining with no evidence of disease at 3 years by Kaplan-Meier method of analysis was 62.1% (95% CI: 0.36-0.87). Accrual and long-term follow-up of large number of surgically treated cases may provide valuable leads to management policies of oral leukoplakia, since, as of now, the added value of specific treatments over and above primary prevention by tobacco and alcohol control remains to be established.