Background Current evidence-based guidelines provide unclear support for many common polypharmacy practices in schizophrenia. Excessive or complex polypharmacy (≥4 psychotropics) has been studied in patients with bipolar disorder, but not in schizophrenia to date. Methods We conducted a digital medical record data extraction of 829 patients consecutively admitted to a psychiatric hospital and diagnosed as having schizophrenia-spectrum disorders. Results In those prescribed psychiatric medication preadmission, 28.1% (n = 169) met the criteria for complex polypharmacy. Complex polypharmacy patients were older, female, white, and disabled, and had more comorbidities compared with those without complex polypharmacy. In multivariable analysis, complex polypharmacy was specifically associated with being white and disabled, and having a comorbid anxiety disorder, tobacco use disorder, metabolic condition, and neurological condition compared with noncomplex polypharmacy patients. Conclusions Although there is little evidence to support complex polypharmacy in schizophrenia, rates were relatively high in patients requiring hospitalization, especially when they are also diagnosed as having comorbid psychiatric and medical conditions. Future research is needed to study the risk-benefit profile for these patients, especially considering their higher medical burden and related health risks.