Background: Topical photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) and methyl aminolevulinate (MAL) as precursors of protoporphyrin IX (PPIX) have been used in skin cancer treatment and other skin diseases. To establish new topical PDT, protocols are necessary first to conduct studies in vivo using animal skin models. The goal of this study is to evaluate the robust correlation between porcine and human skin models in vivo by optical methods to confirm the suitability of porcine skin models to predict drug behavior in the human skin on topical PDT protocols. Methods: The study was performed in vivo using porcine and human skin models. In human skin, ALA and MAL cream mixture samples were applied to the inner arm in a circular area of 1 cm 2 . In porcine skin, the cream was applied on the back in an area of 4 cm 2 , over which an occlusive dressing was placed. PPIX production was monitored for up to 5 h using widefield fluorescence imaging and fluorescence spectroscopy techniques. Results: Human skin models showed similar behavior to porcine skin models, which indicates high similarity between both models and confirms that porcine skin is an adequate model to establish new clinical PDT protocols in human volunteers.