AbstractBackgroundFractional CO2 laser and Nd‐YAG laser have been reported to have promising results in the management of keloids. So far, there have been no comparative studies between these laser modalities.AimsThe study aimed to compare the efficacy of fractional CO2, Nd‐YAG, and a combination of both in the management of keloids.Patients and methodsForty‐five keloid patients were divided into 3 equal groups: the first received fractional CO2 only, the second received Nd‐YAG only, and the third received a combination of both lasers. Each group received its designated treatment every 4 weeks for 4 sessions. The improvement was evaluated by the “Patient and Observer Scar Assessment Scale” (POSAS). Detection of procollagen I mRNA by RT‐PCR analysis was done.ResultsThe assessment by POSAS showed the most significant clinical improvement in the combination group and a less significant improvement in the fractional CO2 group, while the least improvement was seen in the Nd‐YAG group. Molecular assessment via procollagen I yielded matching results.ConclusionThe study showed that the combination of fractional CO2 and Nd‐YAG lasers has a synergistic effect being the most effective in the management of keloids, fractional CO2 being more effective than ND‐YAG and Nd‐YAG being the least effective.