Background: Adherence to treatment is a mayor issue in dermatology, and its relationship to quality of life has barely been studied. Objective: To evaluate the relationship between scores on the Skindex-29 skin disease assessment scale and adherence to treatment in patients with acne. Methods: An observational, prospective study of 1,628 patients carried out by 252 clinicians in Spain. Results: Adherence was related to better objective and subjective severity index scores and better Skindex-29 scale scores at the end of the study. Young, male and unemployed patients had the worst adherence scores. Baseline and final Skindex-29 scale scores were significantly worse in non-adherent females, while non-adherent males scored better. Reasons for non-adherence were side effects for older patients and forgetfulness for younger ones. Conclusion: Dermatologists should explain that adherence to treatment is linked to better outcomes and better quality of life. Young females with high Skindex-29 scale scores and males with low Skindex scores are especially prone to non-adherence.