BACKGROUND: The efficacy of laser treatment for facial café au lait macules (CALMs) is random. AIM: To compare the response of different characteristics of CALMs skin lesions to laser treatment. PATIENTS/METHODS: In this single-center retrospective case series, patients with café au lait macules who received laser treatment between 2015 and 2022 at our clinic were reviewed. A total of 319 consecutive patients were eligible and were treated with either a 755-nm-alexandrite picosecond laser or a quality-switched 755-nm-alexandrite laser. Observers were blinded to the final patient groups. Efficacy was graded according to four levels of treatment response: poor (Grade 1, 0%-25% improvement), fair (Grade 2, 26%-50% improvement), good (Grade 3, 51%-75% improvement), and excellent (Grade 4, 76%-100% improvement). Treatment effects evaluated as Grades 2-4 were considered effective. RESULTS: Of the 319 patients, excellent and good responses were observed in 80 (25.08%) and 66 (20.69%) cases, respectively. Fifty-two patients (16.30%) displayed an outcome of Grade 2 (26%-50% improvement), whereas 121 (37.93%) cases showed an outcome of Grade 1 (0%-25% improvement). The overall treatment effective rate (Grades 2-4) was 62.07%. Binary logistic regression analysis showed a significant association of therapeutic efficacy with lesion distribution (segmental vs. non-segmental CALMs) and lesion border (irregular vs. regular) (p <
0.05 for both). CONCLUSIONS: Segmental and irregular border CALMs tended to respond well to laser therapy. Clinicians can leverage these characteristics to predict efficacy and manage patient expectations more effectively.