Objective: This study aims to compare breast density between two mammograms in women with premature ovarian failure (POF). Methods: A cohort study evaluated 56 women with POF. Two mammograms performed at least 2 years apart were analyzed. Mammogram films were digitalized, and images were assessed using a computer-assisted method; the percentage of breast image that is radiologically dense is referred to as the percentage of mammographic density (PMD). Age at menarche, age at onset of POF, length of POF, length of estrogen-progestin therapy (EPT), body mass index (BMI), pregnancy, and age at the time of each mammogram were evaluated. Results: The mean (SD) age at POF diagnosis was 32.35 (5.95) years. In the first mammogram, the mean (SD) age, BMI, and length of POF were 37.58 (3.72) years, 26.79 (4.86) kg/m, and 5.25 (4.61) years, respectively. EPT had been used for a mean (SD) of 2.71 (3.12) years. In the second mammogram, the mean (SD) age, BMI, and length of POF were 43.23 (4.98) years, 27.6 (5.39) kg/m, and 10.5 (5.11) years, respectively. EPT had been used for a mean (SD) of 7.25 (4.6) years. The mean (SD) interval between mammograms was 5.25 (3) years, and the mean (SD) PMD decreased from 27.78% (21.04%) to 17.53% (15.71%) (P = 0.007). Comparing PMD between women taking EPT and those not taking EPT, we observed no significant differences. In both instances, multiparous women had lower PMD than nulliparous women (P < 0.05). BMI, length of POF, and pregnancy were negatively correlated with PMD. Conclusions: Breast density in young women with POF decreases across a period of 5 years, regardless of EPT use. 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