Treatment goals defined by the absolute Psoriasis Area and Severity Index (PASI) scores offer certain advantages in the clinical setting. In order to investigate potential treatment targets, this study evaluated absolute PASI outcomes relative to other measures of response using data from two randomized clinical trials of patients with moderate-to-severe psoriasis treated with ixekizumab, etanercept, or placebo (n=2,567). Response was assessed throughout 12 weeks as the proportion of patients achieving absolute PASI band cut-offs who also reached established response criteria. Most PASI band ≤2 responders also achieved PASI 90 (70.1–100%), static Physician’s Global Assessment (0,1) (91.3–96.1%), Dermatology Life Quality Index (0,1) (63.0–67.7%), Patient Global Assessment of Disease Severity (0,1) (80.3–86.7%), and Itch Numeric Rating Scale improvement ≥4 (87.2–87.6%). Agreement sharply decreased for less stringent PASI criteria. These data indicate that PASI ≤2 represents significantly meaningful clinical and health-related quality of life improvements and may be a suitable treatment target for moderate-to-severe plaque psoriasis.