Background:Despite evidence that antibiotics may not be necessary to treat acute uncomplicated diverticulitis, they remain the mainstay of treatment in the United States. A randomized controlled trial evaluating antibiotic effectiveness could accelerate implementation of an antibiotic-free treatment strategy, but patients may be unwilling to participate.Objective:This study aims to assess patients’ attitudes regarding participation in a randomized trial of antibiotics versus placebo for acute diverticulitis, including willingness to participate.Design:This is a mixed-methods study with qualitative and descriptive methods.Settings:Interviews were conducted in a quaternary care emergency department and surveys were administered virtually through a web-based portal.Patients:Patients with either current or previous acute uncomplicated diverticulitis participated.Interventions:Patients underwent semi-structured interviews or completed a web-based survey. Main Outcome measures: Rates of willingness to participate in a randomized controlled trial was measured. Salient factors related to healthcare decision-making were also identified and analyzed.Results:Thirteen patients completed an interview. Reasons to participate included a desire to help others or contribute to scientific knowledge. Doubts about the efficacy of observation as a treatment method were the main barrier to participation. In a survey of 218 subjects, 62% of respondents reported willingness to participate in a randomized clinical trial. “What my doctor thinks,” followed by “What I’ve experienced in the past” were the most important decision-making factors.Limitations:There is possible selection bias inherent to using a study to evaluate willingness to participate in a study. Also, the population sampled was disproportionately White compared to the population affected by diverticulitis.Conclusions:Patients with acute uncomplicated diverticulitis maintain complex and varying perceptions of the use of antibiotics. Most surveyed patients would be willing to participate in a trial of antibiotics versus placebo. Our findings support a trial’s feasibility and facilitate an informed approach to recruitment and consent.