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Recently, indoor daylight photodynamic therapy (idl-PDT) has been developed; however, its efficacy and tolerability remain to be assessed. This is a not-inferiority study to compare treatment outcomes of cPDT with a red LED lamp and idlPDT with a polychromatic white LED lamp in adult patients affected by symmetrical AKs of face and/or scalp. In this comparative, intra-patient, split-face, randomized clinical trial forty-three adult patients were enrolled. Two contralateral and symmetrical target areas of the face and/or scalp harboring at least 5 AKs were selected and randomized 1:1 to treatment with cPDT and idlPDT. The AKs number and cumulative area were assessed at baseline (T0). Efficacy and cosmetic outcome were assessed 3 months after treatment (T1). Total AKs number and area reduced significantly with both idlPDT (p <.0001) and cPDT (p <.0001) in comparison to baseline. cPDT was more painful (p <.0001) and induced a more severe inflammation (p <.0001). Twenty-nine patients (70.7%) gave their overall preference to idlPDT (p <.001). idlPDT may represent an alternative treatment protocol to cPDT for in-office treatment of AKs patients with better tolerability and a not inferior efficacy. [ABSTRACT FROM AUTHOR]