OBJECTIVETo test whether a theory-based, literacy, and culturally tailored self-management intervention, Latinos en Control, improves glycemic control among low-income Latinos with type 2 diabetes.RESEARCH DESIGN AND METHODSA total of 252 patients recruited from community health centers were randomized to the Latinos en Control intervention or to usual care. The primarily group-based intervention consisted of 12 weekly and 8 monthly sessions and targeted knowledge, attitudes, and self-management behaviors. The primary outcome was HbA1c. Secondary outcomes included diet, physical activity, blood glucose self-monitoring, diabetes knowledge and self-efficacy, and other physiological factors (e.g., lipids, blood pressure, and weight). Measures were collected at baseline and at 4- and 12-month follow-up. Change in outcomes over time between the groups and the association between HbA1c and possible mediators were estimated using mixed-effects models and an intention-to-treat approach.RESULTSA significant difference in HbA1c change between the groups was observed at 4 months (intervention −0.88 [−1.15 to −0.60] versus control −0.35 [−0.62 to 0.07], P < 0.01), although this difference decreased and lost statistical significance at 12 months (intervention −0.46 [−0.77 to −0.13] versus control −0.20 [−0.53 to 0.13], P = 0.293). The intervention resulted in significant change differences in diabetes knowledge at 12 months (P = 0.001), self-efficacy (P = 0.001), blood glucose self-monitoring (P = 0.02), and diet, including dietary quality (P = 0.01), kilocalories consumed (P < 0.001), percentage of fat (P = 0.003), and percentage of saturated fat (P = 0.04). These changes were in turn significantly associated with HbA1c change at 12 months.CONCLUSIONSLiteracy-sensitive, culturally tailored interventions can improve diabetes control among low-income Latinos; however, strategies to sustain improvements are needed.