BACKGROUND: Supporting patients' decision making about clinical trials may enhance trial participation. To date, few theory-based interventions have been tested to address this issue. The objective of the current study was aimed to evaluate the effect of a multimedia psychoeducation (MP) intervention, relative to a print education (PE) intervention, on patients' decision support needs and attitudes about clinical trials. METHODS: Patients with cancer who were eligible for participation in a National Cancer Institute therapeutic cancer clinical trial were recruited through the nationwide University of Rochester Cancer Center National Cancer Institute Community Oncology Research Program from 2014 to 2016 and were randomized to the MP or PE intervention. Assessments at baseline (before intervention), postintervention, and at a 2-month follow-up visit included patients' decision support needs, attitudes regarding clinical trials, and clinical trial participation. RESULTS: In total, 418 patients with various types of cancer were recruited (ages 26-89 years). Relative to the PE intervention, the MP intervention did not significantly affect decision support needs. However, patients in the MP arm reported significantly more positive attitudes about clinical trials and were more likely to participate in a clinical trial than those in the PE arm (69% vs 62%; P = .01). Furthermore, an improvement in attitudes about clinical trials significantly mediated the effect of the intervention on participation in clinical trials. CONCLUSIONS: The MP intervention was able to improve patient attitudes toward clinical trials compared with the PE intervention, and this improvement led to increased rates of participation in trials. The MP intervention could be disseminated to improve attitudes about clinical trials among patients with cancer.