AbstractBackgroundThe present study explored the acceptability of psilocybin‐assisted group therapy from the perspective of patients with cancer and depression who participated in a clinical trial assessing the safety and efficacy of this novel intervention.MethodsGuided by the conceptual framework of acceptability, the authors conducted semi‐structured interviews with participants of the psilocybin trial. Data were analyzed using template and thematic analyses.ResultsParticipants’ (n = 28) perspectives on the acceptability of the group and simultaneous sessions was generally positive, both in terms of safety and efficacy: first, the groups contributed to increase participants’ sense of safety and preparedness as they were engaging in the therapy; and second, the groups fostered a sense of connection and of belonging, which served to enrich and deepen the meaning of participants’ experience, ultimately opening a dimension of self‐transcendence and compassion. Other subthemes related to factors influencing the acceptability of the group approach included: 1) the importance of the therapeutic framework, 2) the complementary value of individual sessions, 3) disruptive factors related to the group and/or simultaneous setting, and 4) opportunities and challenges related to group size and how to structure interactions.ConclusionsThis study enhances understanding of what promotes acceptability of the psilocybin‐assisted therapy group model for the treatment of MDD in cancer patients.Plain Language Summary We conducted exit interviews with participants of a phase 2 trial of psilocybin‐assisted therapy (PAT) conducted in a community cancer center, to assess the acceptability of a novel psilocybin delivery model combining simultaneous individual therapy and group sessions. Our findings support the acceptability of this intervention and suggest that in addition to being feasible, it might also enhance participants’ perceived safety and efficacy compared to uniquely individual or group delivery models of PAT. Our analysis highlights critical factors conditioning acceptability and suggests new ways PAT may be scaled and integrated into cancer care.