Introduction: Photodynamic therapy (PDT) is an effective treatment of actinic keratosis (AK) and severe photo aging. Day-light PDT (DL-PDT) is considered an alternative of C-PDT with similar efficacy but with significantly lower procedure-associated pain. A new formulation of ALA at “low” concentration (5%) in a thermosetting gel is available for C-PDT or DL-PDT. When used for PDT the incubation time of this gel is in general 2-2.5 hours. This formulation with high content of water could be feasible for application with penetration-empowering dual mask which could optimize and speed-up the penetration of the active compound through the skin. This mask device comes in two layers. The first layer is wet and in contact with the applied gel. The second layer, which is dry and overlaid on the first, allows the key ingredients to penetrate the stratum-corneum utilizing a micro-current circuit using two anodes placed on each side of the mask acting as natural batteries. This mask could reduce the incubation time of the photosensitizer needed to allow adequate skin penetration before the PDT procedure. Study aim: To evaluate in a pilot-study the efficacy and tolerability of DL-PDT with a thermosetting 5% ALA gel applied using a specific mask penetration-enhancer device. Subjects and methods: A total of 15 men aged >50 years with severe actinic damage of the face or scalp were enrolled in this pilot study. ALA 5% gel was applied (2.5 ml) on the face and scalp. The empowering mask was then put on the treatment area with an incubation time of 1.5 hour. A single day-light session of 20-30 minute (according to the UV fluence of the day) was performed. The primary outcome was the evolution of a 7-item actinic damage score (ADS) evaluating: elastosis, hyperpigmentation, telangiectasia, fine wrinkles, deep wrinkles, stellate pseudo-scar, and presence of actinic keratosis lesions. For each parameter, a 4-grade scale score (0=sign absent; 3: sign severe) was calculated. Therefore, the maximum level of ADS was 21. The baseline visit was performed just before the DL-PDT session; the final evaluation visit was performed two months after the DL-PDT session. A patient-assessed procedurerelated pain score using a 4-point scale (0: no pain; 3: severe pain) was performed at the end of the DL-session. Results: Before DL-PDT, the ADS, mean (SD), score was 16 (5). A total of 74 AK clinically relevant lesions were also present at baseline. At the final visit, the ADS score was significantly reduced to 5(5), corresponding to a -69% reduction. AK lesions at the final visit were reduced by 70% (from 74 to 22). DL-PDT was in general very well tolerated. The procedure-related pain score mean (SD) value was 0.5 (0.5). Conclusion: In subjects with severe actinic damage, a single DL-PDT session with ALA 5% thermosetting gel, with penetration-empowering mask application, was very effective and well tolerated in reducing clinical signs of skin photo damage and reducing AK lesion number.