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/Background: The allostatic framework is a theoretical perspective that identifies allostatic load (AL) as a meaningful measure of dysregulation and desynchrony across biological processes due to cumulative stress exposure, thereby increasing disease risk. Research exploring the relationships of AL with sleep quality have yielded inconsistent findings. We examined AL at three visits (2004–2009 [Visit 1], 2009–2013 [Visit 2] and 2013–2017 [Visit 3]) in relation to sleep quality [Visit 3] among urban adults by sex, race and age group. We analyzed data on 1489 Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) participants [59.6% female, baseline age: 48.2 years, 58.5% African Americans] with available data on cardiovascular, metabolic and inflammatory AL markers and Pittsburgh Sleep Quality Index (PSQI) scores. Least squares regression models were constructed to evaluate AL score at Visit 1 (AL v1) and z-transformed probability of higher trajectory in AL score between Visit 1 and Visit 3 (AL traj) as predictors of PSQI score at Visit 3, controlling for demographic, lifestyle and health characteristics at Visit 1. AL traj was generated using group-based trajectory modeling. In fully adjusted models, AL v1 and PSQI score were positively related among men only (β = 0.43, P = 0.001), whereas higher AL traj was associated with PSQI score among women (β = 0.51, P = 0.001), White (β = 0.45, P = 0.011) and African American (β = 0.33, P = 0.014) populations. There were no statistically significant interactions according to age group (<50 vs. ≥ 50). Disparities exist whereby AL trajectory predicted sleep quality among women irrespective of race and baseline AL predicted sleep quality among men. Future studies should examine bi-directional AL-sleep relationships. • 1489 Healthy Aging in Neighborhoods of Diversity across the Life Span participants. • Allostatic load and Pittsburgh Sleep Quality Index scores. • Baseline allostatic load predicted sleep quality among men. • Allostatic load trajectory predicted sleep quality among women irrespective of race. [ABSTRACT FROM AUTHOR]