BACKGROUND/PURPOSE: Literature data suggest that lower fluence rates are preferable in terms of clinical response and tolerability for treating patients with actinic keratoses (AKs). We aimed to clarify the impact of different fluence rates on pain during photodynamic therapy (PDT) for AKs, as well as on treatment outcome.METHODS: Individuals with at least three discrete AKs were recruited. Each lesion was randomly allocated to 25, 50 or 75 mW/cm2 of topical 5-aminolevulinic acid (5-ALA) PDT, using non-coherent light source. Primary end point was pain during illumination, evaluated using a visual analogue scale (VAS). Secondary end points were clinical outcome and adverse events.RESULTS: Fifty adults, with 150 AKs lesions were recruited in the study. Mean VAS score did not significantly differ between the groups of 25 and 50 mW/cm2 (P=0.714). However, mean VAS was significantly higher at the group of 75 mW/cm2 in comparison to the former ones (P=0.000). With respect to the clinical outcome and adverse events during the first year of follow-up, no differences were observed between the three groups. Comparison between the 25 and the 50 mW/cm2 (P=0.749), as well as between the former and the 75 mW/cm2, did not show a dependence of complete response rate on fluence (P=0.749 and P=1.000, respectively).CONCLUSIONS: According to our observations a fluence rate between 25 and 50 mW/cm2 is effective and better tolerated by patients treated with topical 5-ALA PDT for AKs.