Background: Antipsychotic polypharmacy (“polypharmacy”) involves the concurrent prescribing of two or more antipsychotics for managing schizophrenia. It occurs frequently despite there being limited clinical evidence for this practice and an increased risk of adverse events. Little is understood about why it occurs outside of treatment guidelines, highlighting a current research gap. Objective: To explore the factors contributing to non-evidence based polypharmacy practice and possible strategies for addressing these factors. Methods: Three focus groups were conducted between June and August 2018 with doctors and nurses employed at a mental health unit of a Western Australian public hospital. Participants were asked about their perceptions of polypharmacy, why it occurred and what could limit its prevalence. Thematic inductive analysis was mapped to the Theoretical Domains Framework to identify key underlying themes and to establish potential enablers and barriers for practice change. Results: Participants understood the risks of polypharmacy and perceived it to largely be perpetuated by external factors, out of which two key themes emerged: system-related issues (e.g.: communication failures whereby de-prescribing plans are not actioned); and patient-related issues (e.g.: misinformed views translating to medication-seeking behaviour). This led to the third theme: a disconnect between clinicians' knowledge and their practices (i.e.: being aware of Australian evidence-based guideline recommendations yet acknowledging polypharmacy still occurred due to the aforementioned issues). Strategies suggested to address these issues included developing medication management plans to bridge communication gaps and managing patients’ medication expectations with education. Conclusions: Management of schizophrenia is complex, requiring consideration of many patient-related and systemic factors. Polypharmacy has a place in certain contexts, however, must be well considered and closely monitored to allow for early identification of opportunities to rationalise (i.e.: de-prescribe) therapy, where appropriate. Future research objectives will centre on implementing strategies identified from these focus groups to optimise patient outcomes.