High mammographic density is a strong breast cancer risk factor. Density normally declines with aging. We investigated whether the level of decline in mammographic density is related to breast cancer risk using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Prospect cohort. This cohort was recruited among participants of a population-based breast cancer screening program in the Netherlands between 1993 and 1997. We examined whether age-related changes in mammographic density were different for 533 cases and 1,367 controls who were 49-69 years of age at the time of recruitment into the cohort. We used mixed models with linear and quadratic terms for age and interaction terms between age terms and case status. The percent mammographic density at the first available mammogram was higher for cases than for controls (25.2% vs. 22.5%) (P = 0.003). The average decline in density over 10 years was 11% in both cases and controls (P = 0.56). When studying changes among 4 categories of density, we saw some indication that large changes may influence breast cancer risk. Although no difference was seen in the average decline, we cannot exclude that large changes may influence breast cancer risk.