The popularity of laser therapy in acne treatment has been increasing recently due to its safety, effectiveness, and convenience. Both 595-nm pulsed dye laser (PDL) and 1064-nm long-pulsed neodymium:yttrium-aluminum-garnet laser (Nd:YAG) have been successful in treating inflammatory acne lesions. However, clinical data from controlled comparative studies are still lacking. To compare the clinical efficacy of 1064-nm Nd:YAG with 595-nm PDL for the treatment of acne vulgaris. Thirty-four participants with mild to moderate facial acne were enrolled and then randomized to receive three, 2-week interval treatments with 1064-nm Nd:YAG on one side of the face and 595-nm PDL on the other side. Clinical assessments including acne lesion counts, acne erythema grading, and erythema index were performed at baseline, 2nd, 4th, and 8th week. Participants' satisfaction, preference, and adverse effects were recorded. As compared with baseline, the significant reduction of mean inflammatory acne lesion counts, acne erythema grading, and erythema index was demonstrated on 595-nm PDL-treated sides and 1064-nm Nd:YAG-treated sides. However, there were no significant differences between both sides. The participants were satisfied with both laser treatments, but the participants preferred 1064-nm Nd:YAG over 595-nm PDL treatment. The adverse effects were less on 1064nm Nd: YAG-treated sides. 1064-nm Nd:YAG and 595-nm PDL treatments are equally effective in reducing inflammatory acne lesions and acne erythema in mild to moderate facial acne vulgaris.