To date, there is no gold standard therapy for skin photoageing. In the last decade, laser technologies have offered great promise among skin-rejuvenation therapies; however, both non-ablative and ablative fractional resurfacing modalities have their own benefits and drawbacks. More recently, open-label studies and few controlled trials have suggested that photodynamic therapy may have therapeutic potential in photodamage.To assess the efficacy of methyl aminolevulinate + red-light on facial photodamage in a double-blind split-face randomized placebo-controlled trial.Subjects had initially two split-face treatments 2-3 weeks apart in which half of the face was treated with MAL + red-light compared with placebo + red-light. Primary outcome was the assessment of global photodamage 1 month after session 2. Secondary outcomes included the assessment of fine lines, mottled pigmentation, tactile roughness, sallowness, erythema and telangiectasia 1 month after session 2, according to severity scores rated as failure, improvement or success.Based on the intention-to-treat analysis, a total of 48 patients (96 split-faces) were included. Facial global photodamage success or improvement had occurred in 94 split-faces and in no split-faces receiving placebo (RR: 0.02; 95% confidence interval, 0.0-0.14; P = 0.0000). One patient had an adverse event that led to the discontinuation of the therapy after session 1.Methyl aminolevulinate + red-light demonstrated significantly superior efficacy in global facial photodamage compared with placebo. This therapy was also useful for all other specific secondary outcomes, except for telangiectasia. Overall, MAL + red-light sessions were well tolerated and resulted in high/total patient satisfaction in the majority of subjects (80.4%).