OBJECTIVE: Translating evidence-based diabetes prevention interventions to disadvantaged groups is a public health priority that poses unique challenges. Community health centers (CHCs) provide unequaled opportunities to prevent diabetes among poor and minority high-risk groups. This formative study sought to assess structural, processes-of-care (health care quality domains), and patient factors that need to be considered for diabetes prevention at CHCs. RESEARCH DESIGN AND METHODS: A multimethod approach was implemented to assess system-, provider-, and patient-level factors at two large CHCs serving diverse urban communities. RESULTS: Medical chart audits (n = 303) showed limited documentation of risks. Provider surveys (n = 74) evidenced knowledge gaps regarding factors associated with increased diabetes risk, efficacy of pharmacological interventions, and low perceived efficacy in promoting patient behavior change. Patient focus groups (two groups) with at-risk Hispanics and African Americans suggested mixed knowledge regarding whether diabetes can be prevented, some knowledge gaps regarding factors related to risk, and multiple challenges for lifestyle change. CONCLUSIONS: Multiple and multilevel challenges to translating diabetes prevention interventions for the benefit of at-risk populations who seek care at CHCs were observed.