Despite increasing numbers of multiracial individuals, they are often excluded in studies or aggregated within larger race and ethnicity groups due to small sample sizes. To examine disparities in the prevalence of obesity among single-race and multiracial Asian and Pacific Islander individuals compared with non-Hispanic White (hereafter, White) individuals. This cross-sectional study used electronic health record (EHR) data linked to social determinants of health and health behavior data for adult (age ≥18 years) members of 2 large health care systems in California and Hawai'i who had at least 1 ambulatory visit to a primary care practitioner between January 1, 2006, and December 31, 2018. Data were analyzed from October 31, 2022, to July 31, 2023. Self-identified race and ethnicity provided in the EHR as a single-race category (Asian Indian, Chinese, Filipino, Japanese, Native Hawaiian only, Other Pacific Islander, or White) or a multiracial category (Asian and Pacific Islander; Asian, Pacific Islander, and White; Asian and White; or Pacific Islander and White). The main outcome was obesity (body mass index [BMI] ≥30.0), based on last measured height and weight from the EHR. Logistic regression was used to examine the association between race and ethnicity and odds of obesity. A total of 5229 individuals (3055 [58.4%] male; mean [SD] age, 70.73 [11.51] years) were examined, of whom 444 (8.5%) were Asian Indian; 1091 (20.9%), Chinese; 483 (9.2%), Filipino; 666 (12.7%), Japanese; 91 (1.7%), Native Hawaiian; 95 (1.8%), Other Pacific Islander; and 888 (17.0%), White. The percentages of individuals who identified as multiracial were as follows: 417 (8.0%) were Asian and Pacific Islander; 392 (7.5%), Asian, Pacific Islander, and White; 248 (4.7%), Asian and White; and 414 (7.9%), Pacific Islander and White. A total of 1333 participants (25.5%) were classified as having obesity based on standard BMI criteria. Obesity was highest among people who identified as Asian, Pacific Islander, and White (204 of 392 [52.0%]) followed by those who identified as Other Pacific Islander (47 of 95 [49.5%]), Native Hawaiian (44 of 91 [48.4%]), and Pacific Islander and White (186 of 414 [44.9%]). After accounting for demographic, socioeconomic, and health behavior factors, people who identified as Asian, Pacific Islander, and White (odds ratio [OR], 1.80; 95% CI, 1.37-2.38) or Pacific Islander and White (OR, 1.55; 95% CI, 1.18-2.04) had increased odds of obesity compared with White individuals. All single-race Asian groups had lower odds of obesity compared with White individuals: Asian Indian (OR, 0.29; 95% CI, 0.20-0.40), Chinese (OR, 0.22; 95% CI, 0.17-0.29), Filipino (OR, 0.46; 95% CI, 0.35-0.62), and Japanese (OR, 0.38, 95% CI, 0.29-0.50). In this study, multiracial Asian and Pacific Islander individuals had an increased prevalence of obesity compared with many of their single-race counterparts. As the number of multiracial individuals increases, it will be important for clinical and public health systems to track disparities in these populations.