Introduction: Risk of type 2 diabetes mellitus (T2DM) in transgender persons is an area of clinical and research importance. The objective of this analysis was to examine occurrence of T2DM in a cohort of transgender persons receiving gender affirming hormone therapy. Methods: The current analysis uses data from an electronic health record-based cohort study of persons 12 years and older enrolled in three integrated health care systems. The cohort included 3271 transfeminine members matched to 32,366 cisgender women and 32,349 cisgender men, and 2778 transmasculine members matched to 27,422 cisgender women and 27,391 cisgender men. Matching was based on race/ethnicity, year of birth, study site, and calendar year of membership based on the index date (first evidence of transgender status). Cohort ascertainment spanned nine years from 2006 through 2014 and follow up extended through 2016. Data on T2DM incidence were analyzed using Cox proportional hazard models whereas prevalence was compared using logistic regression; all analyses were adjusted for BMI. Type 1 diabetes cases were excluded from the analysis. Results: Incidence of T2DM was similar across all groups overall and in the analyses limited to a subcohort of transgender members receiving gender affirming hormone therapy. At baseline, there was a significant difference in the prevalence of T2DM in the transfeminine cohort versus reference cisgender men (odds ratio 1.80, 95% CL: 1.01 to 3.21, p-value 0.05). No significant differences in prevalence were found across the remaining comparison groups. Conclusion: Transgender people do not appear to be at higher risk for T2DM compared to their cis-gender counterparts regardless of hormone therapy receipt. Disclosure N. Islam: None. M. Goodman: None.