Abstract Background: Endometrial cancer (EC) is the most common gynecologic cancer diagnosed in the United States. With >750,000 survivors in 2014, EC comprises the second largest group of female cancer survivors. Higher body mass index (BMI) and other medical comorbidities have been suggested to negatively impact EC survival; however, data in minority populations with rising EC incidence and mortality (i.e. Asian Americans, African Americans, Latinas, etc.) are scarce. We examined the association of pre-diagnostic BMI and obesity-related comorbidities with overall survival in African-American, Japanese, Native Hawaiian, Latino and white women in the Multiethnic Cohort. Methods: Women with complete risk factor data who developed endometrial cancer during follow up were included in the analysis (N = 998). BMI and obesity-related comorbidities (diabetes, hypertension, heart attack and stroke) were self-reported at cohort entry and at subsequent follow-ups. Cox's models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) with time-varying exposures in relation to all-cause mortality while adjusting for age at diagnosis, tumor characteristics, treatment, and education. Results: The mean age at EC diagnosis was 67.7 ± 8.5 years. The mean follow-up period was 7.3 ± 5.3 years from diagnosis to death or end of follow up during which time a total of 323 deaths were observed, 84 (26%) of which were due to EC. The mean BMI was 29.9 kg/m2 and 53% of women had at least one comorbid condition. The prevalence of obesity and comorbid conditions varied across ethnic groups (P<0.0001). The prevalence of obesity (BMI ≥30 kg/m2) ranged from 18% in Japanese Americans to 69% in Hawaiians. The prevalence of women with at least one comorbid condition ranged from 38% in whites to 76% in African Americans. Women with a BMI ≥35 kg/m2 had an increased risk of all-cause mortality [HR = 1.55 (95% CI: 1.06, 2.28)] compared with women with BMI <25 kg/m2. Women with two or more comorbid conditions also had a higher risk of all-cause mortality (HR = 1.61; 95% CI: 1.12, 2.31) compared to those with no medical comorbidities. There was evidence of ethnic differences in the comorbidity and all-cause mortality association (P interaction = 0.02); the presence of two or more comorbidities was significantly associated with all-cause mortality in whites (HR = 2.98; 95% CI: 1.34, 6.63) and Japanese Americans (HR = 3.47; 95% CI: 1.19, 10.14), but not in African Americans (HR = 0.88; 95% CI: 0.42, 1.82), Latinas (HR = 1.16; 95% CI: 0.45, 2.96), and Native Hawaiians (HR = 0.95; 95% CI: 0.22, 4.02). Conclusions: Our results show that higher pre-diagnosis BMI and the presence of two or more comorbidities increase the risk of overall death among multiethnic women diagnosed with EC. Clear identification and targeted managements of these conditions may improve overall survival after EC diagnosis. Citation Format: Veronica Wendy Setiawan, Gertraud Maskarinec, Yvonne G. Lin, Dongyun Yang, Lynne R. Wilkens, Brian E. Henderson, Loic Le Marchand. Obesity, comorbidity and endometrial cancer survival: the multiethnic cohort. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 882. doi:10.1158/1538-7445.AM2015-882