OBJECTIVES Actinic keratosis (AK) is a common skin condition associated with cumulative sun exposure that may progress to non-melanoma skin cancer. The disease can potentially influence Health Related Quality of Life (HRQoL), but studies of HRQoL in patients with AK are limited. The objective was to analyze HRQoL in patients with AK using generic and disease-specific HRQoL instruments and to analyze the relationship between instruments. METHODS AK patients who visited dermatological clinics in Denmark were included in an observational, cross-sectional, study in a multi-center setting. Dermatologists assessed AK severity and patients completed: Actinic Keratosis Quality of Life Questionnaire (AKQoL), Dermatology Life Quality Index (DLQI), EQ-5D (5L), and EuroQoL Visual Analogue Scale (EQ-VAS). RESULTS A total of 312 patients from 10 clinics were included in the analyses. In general, patients with AK reported impaired HRQoL. The mean values (possible range) were: AKQoL 6.7 (0-27), DLQI 2 (0-30), EQ-5D-5L 0.88 (0-1), and EQ-VAS 79 (0-100). HRQoL was least affected in patients with mild actinic disease, whereas patients with severe actinic damage suffered from further impaired HRQoL (mean AKQoL 10.1 and DLQI 4.6). The correlation between DLQI and AKQoL was moderate (0.52), whereas the correlations between DLQI and EQ-5D (-0.36) and between AKQoL and EQ-5D (-0.10) were weak. CONCLUSIONS All patients with AK had impaired HRQoL. Patients with severe actinic damage were considerably more affected than those with mild disease. Correlations between instruments demonstrate that they are complementary as they measure different aspects of HRQoL and are used for different purposes. EQ-5D is essential for economic evaluations, the DLQI is responsive to changes in relation to treatment and AKQoL captures important aspects related to sun damaged skin.