© 2017 Informa UK Limited, trading as Taylor & Francis Group. Background: The emergence of new biological therapies showing high and sustained level of Psoriasis Area and Severity Index (PASI) 90 response has provided the possibility of both greater skin clearance and increased quality of life (QOL). Objective: To evaluate the association of greater response in skin clearance with improvements in skin-related QOL up to 52 weeks. Methods: Subjects achieving various levels of skin clearance (PASI 90–100 or PASI 75–89) and Dermatology Life Quality Index (DLQI) (0/1) response were compared using ERASURE and FIXTURE trial data. Similar analyses with IGA ratings of Clear or Almost Clear were performed. Results: Significantly more PASI 90–100 responders at week 12 had DLQI 0/1 response than PASI 75–89 (69.4% vs. 47.1%; p <.001) and sustained DLQI 0/1 response at week 52 (74.0% vs. 56.7%; p <.001). IGA results were similar. Conclusions: These results show that PASI 90–100 is a relevant therapeutic goal in moderate to severe psoriasis compared to PASI 75–89 when considering patients’ QOL.