The Skindex-16 questionnaire was recently developed as a measure of dermatological health-related quality of life (HRQoL), including symptoms, emotions and functional aspects. Bepotastine besilate is a selective histamine H(1) -receptor antagonist and a second-generation non-sedating antihistamine to treat various dermatological disorders. We assessed changes of the HRQoL instrument (Skindex-16) on patients with pruritus, including those with atopic dermatitis (AD) over bepotastine treatment period. The patients' personal assessment of the intensity of pruritus was determined using the Visual Analog Scale (VAS) for pruritus. Patients answered the Skindex-16 at baseline and at week 4. Forty-eight of 51 enrolled dermatological patients completed the Skindex-16. Of the 48 patients, 11 had AD and 37 had other conditions. Improvement in the clinical evaluation and VAS score was significant in all patients, the AD group and the other disorders group between baseline and week 4. Skindex-16 showed significantly lower scores for each of the three scales (symptoms, emotions and functioning) and the global score at baseline compared to that at week 4 in all patients and the other disorders. In contrast, there was a significant reduction in the emotions and global score among the AD patients. We found a significant correlation between falls in emotions score of Skindex-16 and falls in VAS scores for pruritus in the AD group. Bepotastine could be effective in the management of patients' HRQoL and useful in patients suffering with pruritus. We suggested that pruritus of AD patients could exert a stronger emotional effect due to the skin condition compared to the symptomatic or functional effects.