Background Polypharmacy is prevalent among long-term care (LTC) residents and can cause significant morbidity. In 2018, we concluded a deprescribing pilot study that reduced potentially inappropriate medication use among LTC residents. Aim We sought to understand the experience and views of physicians, nurses, pharmacists, LTC residents and family members who participated in the pilot study. Method Qualitative semi-structured interviews were conducted with residents and families, a physician, pharmacist and pharmacy student, and licensed-practical nurses. Interviews were audio recorded, transcribed, and analyzed using an inductive thematic analysis approach. Results Interviews with 13 participants yielded themes in 3 categories: (1) views about medication use in LTC and willingness to engage in deprescribing, (2) perceived barriers and enablers for deprescribing, and (3) impact of participating in deprescribing study. Participants were willing to engage in deprescribing; residents were motivated by physician suggestions, and family members prioritized quality of life in decision-making and wanted to be part of the decision-making process. Solutions to overcome barriers included assigning responsibility to identify deprescribing opportunities to pharmacists, scheduling rounds to enable face-to-face team discussions, and consulting families to provide missing medical history to inform deprescribing decisions. Participating in a deprescribing intervention resulted in improved healthcare professional (HCP) confidence and interprofessional collaboration, and caused continued practice change after the study. Conclusion Residents, families, and HCPs are concerned about problems associated with polypharmacy in LTC and are willing to consider deprescribing. Barriers to deprescribing in LTC exist but are not insurmountable. Results provide valuable insight into strategies to optimize deprescribing interventions within LTC.