Background: Laser resurfacing is used to minimize wrinkles, solar scars and sequelae of acne. Objective: Purpose of the systematic review was to compare resurfacing outcomes of CO2 laser and erbium: yttrium aluminium garnet (erb:YAG) laser therapies. Materials and methods: Medline, Cochrane Library, EMBASE and Google Scholar databases were searched until 9 April 2015 using the following terms: laser, carbon dioxide/CO2, facial wrinkles, rhytides and erbium-doped yttrium aluminium garnet/erbium:YAG/Er:YAG. Two-armed controlled split faced studies that compared CO2 laser and erbium:YAG laser in patients with mild-to-moderate facial wrinkles or rhytides were included. Results: The pooled data in this study and findings of other studies support the greater efficacy with the CO2 laser in improving facial wrinkles, but the erb:YAG laser was associated with a better complication profile compared with the CO2 laser. Except one case of hypopigmentation, other complications (i.e., erythema, hyperpigmentation and crusting) and their rates were reported by studies examining both lasers. Conclusion: In general, the CO2 laser appeared to be more efficacious then the erb:YAG laser in treating facial wrinkles. Both lasers treatments were well tolerated.