Clinical trials are considered the gold standard of evidence about the efficacy of cancer prevention, early detection, and treatment interventions. A paucity of data exists on determinants of clinical trial participation in the growing US Latino population despite poor cancer outcomes in this group. This study seeks to describe correlates of awareness of and willingness to participate in clinical trials among largely Central, North, and South American Latinos using safety-net clinics. Between June 2007 and November 2008, we conducted an interviewer-administered, Spanish-language cross-sectional survey (n = 944). Logistic regression was used to assess effects of health information sources and psychosocial variables on awareness of and intention to participate in clinical trials. Analyses were completed in spring 2010. While only 48% knew what a clinical trial was, when explained, 65% indicated a willingness to participate. Providers were the most common source of health information. Use of Internet for health information, trust in health information, and higher education each independently increased the odds of clinical trial awareness, but obtaining information from providers did not. Contacting the Cancer Information Service and psychosocial factors were each independently associated with intent to join a clinical trial, while demographic factors were not. Information channels such as the Internet may be effective in conveying clinical trial information to Latinos. Providers being cited as the most common source of health information but not being associated with knowledge about or intent to participate in trials suggests a missed opportunity for communication to this population.