Background There is a pressing need to address the unacceptable disparities and underrepresentation of racial and ethnic minority groups, including Hispanics or Latinxs, in smoking cessation trials. Objective Given the lack of research on recruitment strategies for this population, this study aims to assess effective recruitment methods based on enrollment and cost. Methods Recruitment and enrollment data were collected from a nationwide randomized controlled trial (RCT) of a Spanish-language smoking cessation intervention (N=1417). The effectiveness of each recruitment strategy was evaluated by computing the cost per participant (CPP), which is the ratio of direct cost over the number enrolled. More effective strategies yielded lower CPPs. Demographic and smoking-related characteristics of participants recruited via the two most effective strategies were also compared (n=1307). Results Facebook was the most effective method (CPP=US $74.12), followed by TV advertisements (CPP=US $191.31), whereas public bus interior card advertising was the least effective method (CPP=US $642.50). Participants recruited via Facebook had lower average age (P=.008) and had spent fewer years in the United States (P<.001). Among the participants recruited via Facebook, a greater percentage of individuals had at least a high school education (P<.001) and an annual income above US $10,000 (P<.001). In addition, a greater percentage of individuals were employed (P<.001) and foreign born (P=.003). In terms of subethnicity, among the subjects recruited via Facebook, a lower percentage of individuals were of Mexican origin (P<.001) and a greater percentage of individuals were of Central American (P=.02), South American (P=.01), and Cuban (P<.001) origin. Conclusions Facebook was the most effective method for recruiting Hispanic or Latinx smokers in the United States for this RCT. However, using multiple methods was necessary to recruit a more diverse sample of Spanish-preferring Hispanic or Latinx smokers.