The acne-specific quality of life (Acne-QoL) questionnaire was developed to measure the impact of facial acne across 4 domains (acne symptoms, role-emotional, self-perception, role-social) of health-related quality of life (HRQL). This analysis assessed the impact of clindamycin phosphate 1.2%-benzoyl peroxide 2.5% (clindamycin-BPO 2.5%) gel on HRQL in a combined study population (N = 2813) of participants with moderate to severe acne vulgaris. Although the results presented within do not include factors of study and study-by-treatment interaction, analyses were performed to confirm that the results were consistent across the 2 identical, double-blind, randomized studies and within each treatment group across studies to justify pooling the data from both studies. The Acne-QoL questionnaire was administered at baseline and at the end of treatment (week 12). Treatment with clindamycin-BPO 2.5% gel significantly improved participant-reported HRQL across all 4 domains compared with individual active ingredients and vehicle (P < .001). The percentage improvement in mean Acne-QoL domain scores with clindamycin-BPO 2.5% gel ranged from 37% to 59%. Because the negative impact of facial acne on HRQL is one of the primary motivators for patients to seek treatment, this analysis underscores the importance of physicians incorporating assessments of HRQL into their clinical decision making.