Study participation bias can impact inferences regarding outcomes. Characteristics of participants and non-participants of two literacy studies conducted in English- and Spanish-speaking cancer patients were compared. Spanish-speaking patients enrolled at a much higher rate than English-speaking patients (91.0% vs. 64.5%, p< 0.001). Multiple imputations technique along with logistic regression analyses showed younger age, higher education, and recruiting from public hospitals were enrollment promoters. Sensitivity analysis using patients with complete data generated similar results. Recruiting sites with more indigent patients and long clinic waiting times had higher enrollment, suggesting that monetary compensation and time availability may be important considerations in study participation. English- and Spanish-speaking patients recruited from same hospitals were also compared.