Context:Recent evidence indicates that thyroid hormones may be closely linked to cognition among adults.Objective:We investigated associations between thyroid hormones and cognitive performance, while testing effect modification by sex, race and elevated depressive symptoms (EDS).Design:This cross-sectional study used extensive data from the HANDLS study.Setting:Baltimore City, MD, 2004-2009.Participants:U.S. adults aged 30-64y. Sample size ranged from 1,275 to 1,346.Main outcome measures:Outcomes included thirteen cognitive test scores spanning domains of learning/memory, language/verbal, attention, visuo-spatial/visuo-construction, psychomotor speed, executive function, and mental status.Results:Within reference ranges, and after Bonferroni correction, elevated free thyroxine (fT4) was associated with better performance on tests of visuo-spatial/visuo-construction ability (overall, women and African-Americans), learning/memory (women and African-Americans); whereas a higher total thyroxine (tT4) level was associated with better performance in the domain of psychomotor speed (individuals without EDS) and a higher level of both fT4 and tT4 was linked to better language/verbal test performance among men. In contrast, higher T3(%uptake) was related to better performance on tests of visuo-spatial/visuo-construction ability and psychomotor speed among Whites. When comparing above reference range to within in the overall population, and after Bonferroni correction, within reference range fT4 was linked to better performance on visuo-spatial/visuo-constrution ability and psychomotor speed, while being below the normal range thyroid stimulating hormone (TSH) level (compared to the reference range) was linked to better performance in domains of psychomotor speed and attention.Conclusions:Thyroid hormones and cognition are closely linked, differentially by sex, race and EDS status.