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Background: Methyl aminolevulinate (MAL) photodynamic therapy (PDT) is commonly used for field treatment of actinic keratoses (AKs). In standard natural daylight PDT (n‐DL‐PDT) the first step, after the application of chemical solar filter, is removal of crusts and scales by curettage, followed by the application of MAL cream. Some patients experience intense pain during curettage and stinging after application of the photosensitizer to just curettaged skin. Objectives: To evaluate whether n‐DL‐PDT without curettage, but preceded by application of keratolytics, would maintain a similar efficacy, based on clinical, dermoscopic, reflectance confocal microscopy (RCM) assessments, safety and patient satisfaction as standard n‐DL‐PDT with curettage. Methods: Forty patients with multiple AKs on the face and/or scalp were enrolled in this study. Patients were randomized into two groups of treatment as follows: (i) MAL n‐DL‐PDT without previous curettage, preceded by skin preparation at home with keratolytics (30% urea cream, twice a day for 7 days; −Cur group) and (ii) MAL n‐DL‐PDT preceded by skin preparation at the hospital with curettage (+Cur group). Results: Thirty‐nine participants completed the study. Four hundred and twenty‐one AKs in −Cur group and 337 AKs in +Cur group were treated. The mean reduction in the number of AK lesions 3 months after the treatment was 10.7 (−54.7%) in the −Cur and 10.4 (−58.7%) in the +Cur group. We found that the differences in terms of efficacy and patient satisfaction comparing the two treatment regimens were not statistically significant. The pain score reported during and after daylight exposure was similar and low in both groups. Moreover, no unexpected adverse events occurred during the trial period. Conclusions: According to our results, curettage is not necessary to obtain the full treatment effect of n‐DL‐PDT. We experienced in a real‐life setting that n‐DL‐PDT protocol could be changed by replacing curettage with keratolytics. [ABSTRACT FROM AUTHOR]