Abstract This paper evaluates the effectiveness of community health workers/promotores (CHWs) in promoting cancer preventive behaviors in the 2011–2013 Education to Promote Improved Cancer Outcomes (ÉPICO) project. The ÉPICO project utilized CHWs to disseminate cancer education to predominately Spanish-speaking Hispanics living in colonias in the Lower Rio Grande Valley of Texas. The CHWs received training to become Texas-certified CHW instructors and specialized training in message tailoring, and they delivered more than 5000 units of resident education on cancer prevention/detection, treatment, and survivorship for breast, cervical, and colorectal cancer. Using panel data to examine overtime changes in cancer knowledge among Lower Rio Grande Valley residents, the evaluation found significant changes from baseline to both times 1 and 2. Additional individual-level analysis indicated that the increase in resident cancer knowledge was predicted by residents’ perceptions of CHW credibility and intention to change their lifestyles. Multilevel analysis also showed that the increase in cancer prevention knowledge among residents was predicted by attributes of the CHWs who taught them. In particular, CHWs with higher education levels had the most impact on residents’ increased knowledge over time. Unexpectedly, CHWs with more years of experience were less effective teachers than their early career counterparts.