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Background. Cognitive decline and dementia are associated with disability and premature death in old age. We examined whether low handgrip strength predicts subsequent cognitive decline in older Mexican Americans. Methods. We worked with a 7-year prospective cohort of 2160 noninstitutionalized Mexican Americans aged 65 years or older from the Hispanic Established Population for the Epidemiological Study of the Elderly (H-EPESE) who had a Mini-Mental State Examination (MMSE) score [greater than or equal to] 21 at baseline. Measures included: (i) sociodemographic factors (age, gender, and education), handgrip strength, and near and distant visual impairment from baseline interview; and (ii) MMSE, body mass index (BMI), and medical conditions (stroke, heart attack, diabetes, depression, and hypertension) from four waves of data collection. Results. Using general linear mixed models, we found a significant trend with scores in the lowest quartile of handgrip strength at baseline to be associated with lower MMSE scores over time (estimate = -1.28, standard error = 0.16; p < .0001). There was a significant handgrip Strength-by-Time interaction with MMSE scores. Participants in the lowest handgrip strength quartile had a greater cognitive decline over time (estimate = -0.26, standard error = 0.07; p < .001) than did those participants in the highest quartile. This association remained statistically significant after controlling for potential confounding factors. Conclusion. Older Mexican Americans with reduced handgrip strength at baseline demonstrated a statistically significant decline in cognitive function over a 7-year period. By contrast, participants in the highest handgrip strength quartile maintained a higher level of cognitive function.