Background: Despite various treatments attempts, no prospective studies have compared the different therapeutic modalities for treatment of idiopathic guttate hypomelanosis (IGH). This study aimed to compare the efficacy of CO₂ fractional laser (CO₂FL), Er:YAG fractional laser (EYFL), and 0.025% topical tretinoin for treating IGH. Materials and Methods: A total of 122 lesions were analyzed from 18 patients (mean age, 70.00 ± 20.00 years). Treatment outcome evaluations included the visual analog scale (VAS) to assess lesion severity, investigator's global assessment (IGA) to assess the extent of improvement, and patient's satisfaction score (PSS). Results: Among the 122 lesions, 42, 40, and 40 were assigned to the CO₂FL, EYFL, and topical tretinoin treatment groups, respectively. The VAS score was significantly improved after the second treatment. CO₂FL and EYFL therapy had superior treatment efficacy compared to topical tretinoin (p < 0.01 in VAS, IGA, and PSS). There was no significant difference between the two types of fractional lasers. Conclusions: Ablative fractional laser (AFL) was an effective treatment with a relatively short treatment time without serious adverse events. We recommended AFL to treat IGH as an active treatment strategy.