The prevalence of type 2 diabetes is disproportionately high among Asian Indians (AI), one of the fastest growing immigrant groups in the United States (US). Poorly controlled diabetes associated with inadequate self-management increases complications and thus medical costs. Acculturation may be an important determinant of diabetes self-management and hence control. This study examined the association between the degree of acculturation and glycemic control as measured by Hemoglobin A1c in AI adults with type 2 diabetes. A mixed method (quantitative and qualitative) study was conducted among 30 AI adults with type 2 diabetes. Acculturation assessment using the Suinn-Lew Asian Self-identity Instrument was followed by socio-demographic questions, self-reported anthropometric measures, and open ended diabetes self-care questions. A two-step multiple regression analysis and content analysis of verbatim interview transcriptions were conducted. Interactions of acculturation with body mass index (interaction b = 1.11; p = 0.01), annual household income (interaction b = 7.19; p = .01), and diabetes duration (interaction b = .30; p = .02) significantly predicted higher HbA1c levels (R(2) change = .368; F change = 4.21; p = .02). From the qualitative interviews, the following were regarded as US specific facilitators for glycemic control: excellent health care system and facilities, availability of healthy food choices and self-monitoring devices, medical insurance benefits, good quality medications, and improved health awareness. Cultural orientation might be important for patient tailored interventions targeting AI with type 2 diabetes. Therefore, interventions targeted at Asian Indians with diabetes should include culture specific adaptations to nutrition education and support.