To determine whether serum calcium is associated with cognitive function in elderly individuals in the general population. Prospective follow-up study of two independent, population-based cohorts. The Rotterdam Study (median follow-up 11 years) and the Leiden 85-plus Study (median follow-up 5 years). Three thousand nine hundred ninety-four individuals, mean age 71, from the Rotterdam Study and 560 individuals, all aged 85, from the Leiden 85-plus Study. Global cognitive function was assessed in both cohorts using the Mini-Mental State Examination; attention, psychomotor speed, and memory function were assessed in the Leiden 85-plus Study only. Linear regression and linear mixed models were used for statistical analyses. In the Rotterdam Study, high serum calcium was associated with worse global cognitive function at baseline (P<.05) and a faster rate of decline in cognitive function during follow-up (P=.005) in individuals aged 75 and older but not in younger individuals. In the Leiden 85-plus Study, high serum calcium was associated with worse global cognitive function from age 85 through 90 (P<.001). This observation also held for the specific cognitive domains tested (all P<.01). These results did not change when individuals with serum calcium levels greater than normal (>2.55 mmol/L) were excluded from the analyses. In the general population, high serum calcium levels are associated with faster decline in cognitive function over the age of 75.