Melasma is an acquired pigment disorder showing symmetrical hyperpigmentation of the face characterized by light to dark brown patches with indistinct borders on both cheeks. Melasma is prevalent in middle-aged women with harmless hormone imbalances. It is also known as the mask of pregnancy and is prevalent in most child-bearing women. It fluctuates month by month, and yet, there is no promising treatment. The Q-switched neodymium-doped yttrium aluminum garnet (QS-Nd:YAG) laser (1,064-nm wavelength) was introduced in Asia years ago for both skin toning and treatment of facial pigment. This low-fluence, 1,064-nm QS-Nd: YAG laser also reportedly improved melasma. Adjunctive treatments such as vitamin C iontophoresis or chemical peels were recommended in other reports. The technique using the 1,064-nm QS-Nd:YAG laser for toning and the enhancement of adjunctive treatments need further investigation and long-term follow-up before recommendations for the ideal protocol for melasma treatment can be made. The aim of this study is to evaluate the improvement of melasma using different parameters with the 1,064-nm QS-Nd:YAG laser with ultrasonic application of topical vitamin C. Eight patients, ranging in age from 32 to 45 years (mean 37 years), with long-term melasma were studied. Most of the melasma cases were dermal or mixed-type melasma. The patients had no cosmetic treatment (laser, intense pulsed light, or chemical peel) 1 year prior to the study. The entire face of each patient was treated with the 1,064-nm QS-Nd:YAG laser for four sessions at 1-month intervals. The laser treatment was divided into three parts with different parameters. First, each patient underwent whole face exposure for one pass with an 8-mm spot size at a power of 2.0 J/cm(2). Next, the spot size was shifted to 6 mm at a power of 3.5 J/cm(2) for one full-face pass, and then ended with a 4-mm spot size at 3.2 J/cm(2) for one full-face pass, with multiple passes for the main lesions. The end point was mild erythema and swelling, without petechiae. All patients applied ice packs for 5 min before the adjunctive treatment. We designed a split-face study with or without ultrasonic application of topical vitamin C. Only the right side of the face received ultrasonic melasma application of vitamin C for 15 min after ice packing. The left side of the face was covered with a moisturizing lotion. Objective evaluation was performed with visual analog score. All eight patients completed the 3-month follow-up after the four laser treatments. Statistics showed significant improvement with ultrasonic application of vitamin C compared to laser monotherapy. The improvement was more pronounced during second to fourth sessions. There was no rebound or post-inflammatory hyperpigmentation detected during the 3-month follow-up period. The combination of 1,064-nm QS-Nd:YAG laser treatment with ultrasonic application of topical vitamin C exerted more prompt response of melasma. We recommended this protocol including mixed parameters of 1,064-nm QS-Nd:YAG laser toning method combining with vitamin C ultrasonic application that can yield higher satisfaction for the difficult facial pigmentation problems such as melasma.