OBJECTIVES: The objective of this analysis was to examine the impact of ustekinumab on health related quality of life (HRQoL) in psoriasis patients. METHODS: 766 patients were enrolled in the PHOENIX I trial. Patients were randomized to placebo, ustekinumab 45 mg, or ustekinumab 90 mg. Patients received ustekinumab at baseline, week 4, and q12w thereafter. Patients randomized to placebo received placebo at baseline and week 4, and ustekinumab 45 mg or 90 mg after cross-over at week 12. HRQoL were assessed using the SF-36 and Dermatology Life Quality Index (DLQI). RESULTS: Baseline SF-36 and DLQI scores were similar among treatment groups with a mean PCS score of 47.9, mean MCS score of 49.8, and mean DLQI score of 11.5. Compared with the placebo group, patients in each ustekinumab group had significantly greater improvements from baseline in both the PCS (2.0 and 3.2, vs. –0.5, p<0.001) and MCS scores (2.1 and 2.5 vs. –1.3, p<0.001) at week 12. All 8 domains of the SF-36 showed statistically significant improvements (p<0.05) in the combined ustekinumab group versus placebo at week 12. At week 12, the mean change from baseline in DLQI was –8.0 for the 45 mg group and –8.7 for the 90 mg group versus -0.6 for the placebo group (each p<0.001 vs. placebo). A greater proportion of patients in each ustekinumab group than in the placebo group achieved a clinically meaningful improvement in PCS and MCS scores (≥5-point improvement), and a DLQI score of 0 or 1 at week 12. These improvements observed in the ustekinumab groups were maintained through week 40. Patients in the placebo group who crossed-over to ustekinumab at week 12 achieved improvements in PCS, MCS and DLQI scores at week 40 that were similar in magnitude to those observed in patients initially randomized to ustekinumab. CONCLUSIONS: Ustekinumab treatment significantly improves overall and disease-specific quality of life in moderate to severe psoriasis patients.