Abstract Mammographic density is an independent risk factor for breast cancer and has been shown to differ among populations with varying risk to breast cancer. We sought to compare the distribution of known breast cancer risk factors between an Asian and a Caucasian population, and to determine if the variations in mammographic density between Asian and Caucasian populations can be attributed to the differences in the distribution of these risk factors. 2948 women with no personal history of breast cancer attending an opportunistic screening program in Malaysia (MyMammo) were included in the analysis. Participants were age and BMI matched to 8837 women of the Karolinska Mammography Project for Risk Reduction of Breast Cancer (KARMA) study in Sweden. For analyses involving mammographic density, a subset of Malaysian women with available raw FFDM images (n = 1501) and matched Swedish women (n = 4501) were included for analysis. Volume-based mammographic density measurements for both cohorts were measured using an automated method (Volpara). Descriptive statistics were used to describe the distribution of breast cancer risk factors and mammographic density measures between the two cohorts. General linear models and stepwise selection method were used to determine the risk factors associated with mammographic density within each cohort. Most of the anthropometric, reproductive and lifestyle risk factors examined were differentially distributed between the two cohorts. There was a significantly greater proportion of postmenopausal Swedish women (56%) compared to Malaysian women (51%). Hormone replacement therapy and oral contraceptive ever use was substantially higher among Swedish women (24% and 73%) than Malaysian women (14% and 29%). Mean dense volume was not significantly different between the two cohorts, but Swedish women had a significantly higher mean non-dense volume and lower percent volumetric density compared to Malaysian women. However, pre-menopausal Malaysian women had statistically significant higher dense volume than Swedish women (mean dense volume of 73.9cm3 compared to 70.4cm3). Among post-menopausal women, Malaysian women had significantly lower dense volume than Swedish women (mean dense volume of 54.7cm3 compared to 57.5cm3). In multivariable analyses, age, BMI and parity were associated with dense volume in both cohorts, but regular alcohol intake, height, changes in body shape over time, and menopausal status were only significantly associated with dense volume for Swedish women. In an age and BMI matched cohort, pre-menopausal Asian women had significantly higher dense volume than Caucasian women, whereas, post-menopausal Asian women had lower dense volume than Caucasian women. Population differences in height, body shape changes over time, and alcohol intake could explain, in part, the variation seen in mammographic density, and potentially breast cancer risk, across populations. Citation Format: Nadia Rajaram, Shivaani Mariapun, Mikael Eriksson, Jose Tapia, Pui Yoke Kwan, Weang Kee Ho, Faizah Harun, Nor Aishah Mohd Taib, Per Hall, Soo-Hwang Teo. Lifestyle determinants of mammographic density in Asian and Caucasian populations: A comparative analysis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1740.