The aim of this study was to examine if cessation of smoking after surgical excision of oral potentially malignant lesions in smokers reduced the risk of recurrences, development of new lesions or malignancies. 51 patients with oral leukoplakia or erythroplakia were included. They were daily smokers at the time of diagnosis and were treated surgically. Patients were advised to quit smoking at each visit. The change of smoking habits and occurrence of unfavorable events were noted during follow-up. Descriptive statistics, Fischer's exact test, Kaplan-Meier curves with log-rank test, and Cox proportional hazards model were used for analysis. 16 patients (31%) quit smoking during the observation period. Only one quitter (6%) developed recurrence compared with 11 continuing smokers (33%) (p<0.05). There were no new lesions and no malignancies among quitters compared with 8 new lesions (p<0.05) and 5 carcinomas (p>0.05) in continuing smokers. Multivariate analysis showed continuing smoking to be the most significant factor for occurrence of unfavorable events, OR 23.7. In conclusion, cessation of smoking significantly reduced the risk of unfavorable events after surgical treatment of oral potentially malignant lesions in smokers.