BackgroundTopical photodynamic therapy (PDT) is an established treatment modality for various dermato-oncologic conditions. In Europe, initially requiring irradiation with red light, PDT of actinic keratosis (AK) can now also be carried out with exposure to daylight that has been clinically proven to be as effective as and less painful than red light. ObjectivesIn this paper, we propose a comparison between the conventional protocol for Aktilite CL 128 (red light source) PDT and the European consensus protocol for daylight PDT — with the exposure is assumed to be performed during either a clear sunny day or an overcast day — in the treatment of AK with methyl aminolevulinate through a mathematical modeling. MethodThis already published modeling that is based on an iterative procedure alternating determination of the local fluence rate and updating of the local optical properties enables to estimate the local damage induced by the therapy. ResultsThe European consensus protocol for daylight PDT during a sunny day and an overcast day provides, on average, 6.50 and 1.79 times higher PDT local damages at the end of the treatment than those obtained using the conventional protocol for Aktilite CL 128 PDT, respectively. ConclusionsResults analysis shows that, even performed during an overcast day, the European consensus protocol for daylight PDT leads to higher PDT local damages than the efficient conventional protocol for Aktilite CL 128.