Objective: To assess the effectiveness of a Spanish-language version of the Stanford Chronic Disease Self-management Program among adults who received medical care in community health centers in Mexico.Methods: This was a prospective, randomized study with Mexican users of community health centers in Tampico, Mexico, conducted between September 2015 and July 2016. A total of 120 adults aged 18 years or older were randomly assigned to intervention (n = 62) and control (n = 58) groups. Data were collected at baseline and at 3 and 6 months post intervention using a structured questionnaire. A repeated measures ANOVA was used for data analysis.Results: Statistically significant differences were found in intervention participants at 3 and 6 months post intervention compared to baseline and the control group for self-management behaviors, including: social activity limitation, quality of life perception, depression, stress, physical activity, communication with physicians, adherence to physician visits, and self-management behaviors.Conclusions: Chronic disease self-management programs (CDSMP) with Mexican adults in community settings are effective in improving their health and self-management behaviors. Further research is needed to assess CDSMP in Mexico and Latin America using objective measurements and examining health outcomes and self-management maintenance over longer periods of time.