Conventional photodynamic therapy (cPDT) using red light is considered one of the most effective therapy option for the treatment of actinic keratosis (AK). The main disadvantage of cPDT is the pain experienced by the patients during illumination. Daylight PDT (dPDT) represents an effective and painless alternative. It can be speculated that a combination of both regimes combines their benefits. To compare the combination of cPDT and dPDT (combPDT) to dPDT alone in terms of effectiveness and safety. The study was developed as a single-centre, intraindividual, retrospective study. Each patient received one dPDT and a combPDT session with BF-200 ALA. Primary effectiveness endpoints included the reduction in the number of basal AK, percentage of patients with complete response (CR) and partial response (PR). Safety parameters evaluated were local skin response (LSR) and visual analogue scale (VAS). A total of 19 patients with 264 AK were evaluated 12 weeks after both PDT modalities. The area treated with combPDT showed a reduction in the number of AK lesions (82.7%) when compared to the dPDT-treated area (56.8%). Higher rates of CR (31.6% vs 15.8) and PR (63.2% vs 26.3%) were achieved in combPDT fields. Areas treated with combPDT showed enhanced local skin reactions (LSR) in comparison with dPDT-treated areas (6.4 vs.4.4, respectively). In combPDT-treated patients a moderate increase of the pain during illumination was observed when compared to dPDT (VAS: 3.4 vs 0.6). This study reports the first data set on the benefit of a direct combination of daylight and subsequent conventional red light illumination (combPDT) with BF-200 ALA. The combination approach achieved a significant increase in clearance rates of AK lesions, while pain was perceived as mild to moderate during red light illumination.