Background: Validity of the Pittsburgh Sleep Quality Index (PSQI) has not been established for midlife women before menopause, and evidence suggests that two-factor or three-factor models may be more informative than the PSQI global score derived from its seven components. We hypothesized that the PSQI and its factor structure would be valid in premenopausal women. Materials and Methods: We performed a validation study of the PSQI against wrist actigraphy in a community-based convenience sample of 71 healthy premenopausal women (aged 40-50 years). For convergent validity, PSQI and its component scores were compared with homologous actigraphy measures. For discriminant validity, characteristics known to affect sleep quality were compared, including body mass index, exercise, menopausal status, menopausal symptoms, and depressive symptoms measured with the Center for Epidemiological Studies-Depression (CES-D) Scale. Results: The PSQI global score and Components 1 (quality) and 5 (disturbance) were correlated (p < 0.05) with actigraphy-measured wake after sleep onset. The PSQI global score and Components 1 (quality) and 7 (daytime dysfunction) were correlated with CES-D scores. PSQI Components 2 (onset latency) and 4 (efficiency) were not congruent with homologous actigraphy measures, while component 3 (duration) was congruent with actigraphy duration. The single-factor PSQI global score had a higher McDonald's omega (0.705) and Cronbach's alpha (0.702) than the two-factor or three-factor models. Conclusions: The PSQI global score is a valid measure of sleep quality in healthy midlife women, performing better than two-factor or three-factor models. However, overlapping CES-D and PSQI scores warrant further clinical assessment and research to better differentiate poor sleep quality from depression.