Objective. To investigate the relationship between changes in clinical rating scale items and endpoint Patient Global Impression of Improvement (PGI-I). Methods. Data were pooled from 4 randomized, double-blind, placebo-controlled studies of duloxetine in patients with fibromyalgia (FM). Variables included in the analyses were those that assessed symptoms in FM domains of pain, fatigue, sleep, cognitive difficulties, emotional well-being, physical function, and impact on daily living. The association of endpoint PGI-I with changes from baseline in individual variables was assessed using Pearson product-moment correlations (r). Stepwise linear regression was used to identify those variables for which changes from baseline were statistically significant independent predictors of the endpoint PGI-I ratings. Results. Changes in pain variables and interference of symptoms with the ability to work were highly correlated (r ≥ 0.5 or r ≤ -0.5) with endpoint PGI-I. Moderate correlation with endpoint PGI-I (0.30 ≤ r < 0.5 or -0.5 < r ≤ -0.30) included changes in variables that assessed physical functioning, depression, anxiety, fatigue, and several variables related to impact on daily living. Independent predictor variables of endpoint PGI-I identified by stepwise linear regression included assessments for pain, physical function, vitality, anxiety, social function, and tender point thresholds. Conclusion. In addition to pain reduction, what makes patients with FM feel better may include improvement in fatigue, physical functioning, mood, and impact on daily living. An assessment of these domains may be important in clinical trials of FM and in the management of patients with FM. The Journal of Rheumatology Copyright © 2009. All rights reserved.