Background: Discussing CPR preferences with patients with advanced cancer who are hospitalized is a critical component of end-of-life decision making. However, these discussions are challenging and often avoided by clinicians. We examined the impact of a CPR video decision tool on patients’ choices and knowledge about CPR, and their comfort with watching the video. Methods: We conducted a multi-center randomized controlled trial of 116 patients with advanced cancer hospitalized at two academic oncology centers. We randomized patients to either a 3-minute video describing CPR (n = 52) or standard-oncology care (n = 64). The primary outcome was participants’ preferences for CPR (immediately after viewing the video in the intervention arm). Secondary outcomes included patients’ knowledge (using 5-item questionnaire with higher score reflects greater knowledge), and intervention participants’ comfort with watching the video. Results: The mean age was 66 years (SD = 12); 50% were women, 84% were white, and 48% had lung or gastrointestinal cancer. Only 47% of study participants reported having a discussion about their CPR preferences at the time of admission to the hospital. At baseline, there were no differences in patients’ preferences for not wanting CPR between the intervention and control arms (63% vs. 58%, P = 0.79). After the intervention, participants randomized to the video were more likely not to want CPR (81% vs. 58%, P = 0.03) and were more knowledgeable (mean knowledge score 4.3 vs. 3.2, P < 0.0001) versus control participants. In the intervention arm, 81% of participants found the video helpful, and 94% felt comfortable watching it and would recommend it to others. Conclusions: Seriously ill hospitalized patients with advanced cancer who watched a CPR video decision support tool were more likely not to want CPR and were better informed about their options. Participants reported feeling comfortable watching the video and would recommend it to others facing similar decisions. Video decision support tools can facilitate end-of-life decision-making for hospitalized patients with advanced cancer. Clinical trial information: NCT01527331