Café-au-lait macules (CALM) are benign birthmarks presenting as uniformly pigmented, well demarcated, brown patches that can be distressing to patients, especially when located in cosmetically sensitive areas. As with all pigmentary lesions in skin of color patients, CALMs have been particularly challenging to treat. Here we present the first case series characterizing treatment parameters and clinical outcomes utilizing the 730-nm picosecond titanium sapphire laser for the treatment of CALMs. This device provides an additional safe and effective treatment option for these challenging cases. We performed a retrospective review of patients treated at a single institution between April 2021 and December 2023. Clinical photographs were graded by 3 outside board-certified dermatologists using a 5-point visual analog scale. Fourteen patients (age range: 10 months-66 years, mean age: 27.4 years, Fitzpatrick skin types II-VI) were treated for CALM on the face (11) or body (3). On average, patients received 4.3 treatments, with treatment intervals ranging from 4 to 40 weeks. Treatment remains ongoing with the 730-nm picosecond laser for eight patients. Overall, patients were rated to have a mean improvement of 26%-50%. Two patients (FST III and VI) achieved 100% clearance after 4-5 treatment sessions. Our study included four patients whose CALM were of the smooth bordered "coast of California" subtype, three of whom had a mean improvement rating of only 1%-25%. The fourth patient had near complete resolution. Follow up for these patients has ranged from 6 weeks to 1.5 years. Of the patients treated, one patient experienced transient post-inflammatory hyperpigmentation and another transient post-inflammatory hypopigmentation, while a third patient experienced mild persistent guttate hypopigmentation. Three patients experienced partial recurrence indicating that maintenance treatments may be needed in some patients. The 730-nm picosecond titanium sapphire laser is a safe and efficacious treatment option, in the right morphologic setting, to improve the cosmetic appearance of CALMs in a wide range of ages and skin types. To our knowledge, this is the first reported treatment of CALMs with picosecond lasers in FST V and VI patients. Our study also supports prior studies which have found that CALM with smooth-bordered "coast of California" morphology have a poor response to laser therapy as compared to those with jagged or ill-defined bordered "coast of Maine" morphology.