Objective: The aim of this study was to compare conventional surgery with carbon dioxide (CO2) laser in patients with oral leukoplakia, and to evaluate the postoperative pain and swelling. Study design: A total of 48 patients (27 males and 21 females) with a mean age of 53.7 ± 11.7 years and diagnosed with oral leukoplakia were randomly assigned to receive treatment either with conventional surgery using a cold knife or with a CO2 laser technique. A visual analog scale (VAS) was used to score pain and swelling at different postoperative time points. Results: Pain and swelling reported by the patients was greater with the conventional cold knife than with the CO2 laser, statistically significant differences for pain and swelling were observed between the two techniques during the first three days after surgery. Followed by a gradual decrease over one week. In neither group was granuloma formation observed, and none of the patients showed malignant transformation during the period of follow-up. Conclusions: The CO2 laser causes only minimal pain and swelling, thus suggesting that it may be an alternative method to conventional surgery in treating patients with oral leukoplakia.