Abstract The association between changing body mass index (BMI) and mammographic breast density is important to better evaluate how to adjust for BMI gain/loss in longitudinal studies of density and breast cancer risk. Increasing BMI has been associated with decreasing percent dense area but the effect on absolute dense area is unclear. No studies have explored a longitudinal association using volumetric density measurement. Methods: We examined the association between change in BMI and change in volumetric breast density among 24,556 women who received breast imaging at the San Francisco Mammography Registry from 2007–2013. Height and weight were self-reported at the time of mammography. Breast density was assessed using single x-ray absorptiometry (SXA) volumetric measurement. The cross-sectional and longitudinal associations between BMI and absolute dense volume (DV) and percent dense volume (PDV) were assessed using multivariable adjusted regression. Results: Women were primarily Caucasian (66%) or Asian (25%) and most were postmenopausal (64%) at time of first mammogram. In cross-sectional analysis, BMI was positively associated with DV (β = 2.95 cm3, 95% CI, 2.69–3.21) and inversely associated with PDV (β = −2.03%, 95% CI, −2.09–−1.98). In longitudinal analysis, an annual increase in BMI was associated with an annual decrease in both DV (β = −1.01 cm3/year, 95% CI, −1.59–−0.42) and PDV (β = −1.17%/year, 95% CI, −1.31–−1.04). Findings were consistent between pre- and postmenopausal women. The annual decrease in DV was strongest among premenopausal women who were initially overweight or obese (P < 0.01 for interaction by initial BMI). Conclusion: Our findings support an inverse association between change in BMI and change in PDV. Longitudinal studies of PDV and breast cancer risk, or those using PDV as an indicator of breast cancer risk, should consider adjusting for change in BMI. The association between increasing BMI and decreasing DV is unexpected and will require confirmation using volumetric methods.