The effect of combined 585/1,064-nm (sequential dual-wavelength pulsed dye laser (PDL) and neodymium-doped yttrium aluminium garnet) laser therapy for acne vulgaris has not been evaluated. To compare the efficacy and safety of PDL and of combined 585/1,064-nm laser treatment for mild to moderate facial acne. A 12-week, randomized, prospective, split-face, double-blind study was performed. Sixteen participants with mild to moderate acne were treated with a single pass of a combined 585/1,064-nm laser on half of the face and PDL on the other half during each treatment session. Patients underwent three treatment sessions at 2-week intervals and were followed up at 8 and 12 weeks after treatment commencement. At the final visit, inflammatory acne lesions were reduced by 86% on the PDL sides and by 89% on the 585/1,064-nm laser sides. Noninflammatory acne lesions showed corresponding reductions of 69% and 64%, respectively. A significant difference between the two treatments was observed for noninflammatory acne lesions at the eighth week. Histopathologic examinations showed that both treatments decreased inflammation and interleukin-8 expression and increased transforming growth factor beta expression. PDL and combined 585/1,064 nm laser were safe and effective for the treatment of inflammatory and noninflammatory acne lesions. The authors have indicated no significant interest with commercial supporters.