Abstract Purpose To describe emotional barriers and facilitators to deprescribing (the planned reduction or discontinuation of medications) in older adults with cancer and polypharmacy. Methods Virtual focus groups were conducted over Zoom with 5 key informant groups: oncologists, oncology nurses, primary care physicians, pharmacists, and patients. All groups were video- and audio-recorded and transcribed verbatim. Focus group transcripts were analyzed using inductive content analysis, and open coding was performed by two coders. A codebook was generated based on the initial round of open coding and updated throughout the analytic process. Codes and themes were discussed for each transcript until consensus was reached. Emotion coding (identifying text segments expressing emotion, naming the emotion, and assigning a label of positive or negative) was performed by both coders to validate the open coding findings. Results All groups agreed that polypharmacy is a significant problem. For clinicians, emotional barriers to deprescribing include fear of moral judgment from patients and colleagues, frustration toward patients, and feelings of incompetence. Oncologists and patients expressed ambivalence about deprescribing due to role expectations that physicians “heal with med[ication]s.” Emotional facilitators of deprescribing included the involvement of pharmacists, who were perceived to be neutral, discerning experts. Pharmacists described emotionally aware communication strategies when discussing deprescribing with other clinicians and expressed increased awareness of patient context. Conclusion Deprescribing can elicit strong and predominantly negative emotions among clinicians and patients which could inhibit deprescribing interventions. The involvement of pharmacists in deprescribing interventions could mitigate these emotional barriers. Trial registration ClinicalTrials.gov Identifier: NCT05046171. Date of registration: September 16, 2021.