The picosecond lasers have shown to effectively treat tattoo pigments that are intractable to previous multiple Q-switched (QS) laser treatments. Therefore we hypothesized that a picosecond laser would show better efficacy with minimal adverse events in the treatment of melasma and post-inflammatory hyperpigmentation (PIH) that are difficult to treat with conventional QS lasers. Two patients with melasma and one patient with PIH were treated with a Picosecond 755-nm Alexandrite Laser (Cyanosure, USA). All patients were Korean with skin type IV and no longer responding to QS laser treatments. Laser treatment was well tolerated in all the patients. Adverse events such as PIH were not reported during 8 weeks of follow up period. After the multiple treatment sessions, one patient reported fair improvement and two patients reported good improvement. Consistent with the clinical results, ex vivo skin model irradiated with a Picosecond 755-nm Alexandrite Laser also showed decreased epidermal keratinocyte necrosis compared with the 532-nm QS Neodymium-Doped Yttrium Aluminium Garnet Laser (Lutronic, Korea) yet decreased melanin content. In conclusion, the Picosecond 755-nm Alexandrite Laser may be useful for effective treatment of intractable melasma and PIH with fewer adverse events in dark Asian skin.