Background: The treatment of keloid has been a challenge, and at times, frustrating because of the recurrence. Hence, it is essential to find treatment modality with least recurrence and good cosmetic results. This study showed the effect of topical 5-fluorouracil following carbon dioxide laser excision on recurrence of keloid. Aim: To evaluate the efficacy of combination of carbon dioxide laser and topical 5-flourouracil(5%) in prevention of recurrence of keloid. Material and methods: Total 24 patients (20 females and 4 males) of age group 12-56 years having keloid of duration 1-8 years were included in this study. Lesions were present on ear lobes, shoulder, chest, leg. CO2 laser was used in continuous mode to excise the lesions and all patients advised topical 5-FU(5%) once daily application over the lesion in the night, once re-epithelization started, for 4 weeks. The patients were followed up initially at every week for 4 weeks then every 4 weeks for 24 weeks to evaluate the response of treatment. Result: Of the 24 patients evaluated at 24 weeks, none (0%) showed any sign of recurrence. Out of 22 patients four(18.2%) patients complained of burning sensation/irritation. Three (13.6%) patients of erythema and erosion which cleared with temporary discontinuation of topical 5-FU and completed the 4 weeks of topical therapy. Three (13.6%) patients developed hypopigmentation. Conclusion: Though response of this combination is encouraging in prevention of recurrence of keloid, recurrence on long term follow up need to be observed.