Patients with serious psychiatric disorders, such as schizophrenia and bipolar disorder, often require high-risk medications and experience medical comorbidities. This cohort study assessed the frequency of preventable adverse events during medical hospitalizations in patients with serious mental illness. Preventable adverse events, primarily medication errors, were very common among these patients and were associated with physical injury during hospitalization. The study could not assess the causes of the adverse events, but prior studies have shown that medication administration errors are frequent in psychiatric inpatients. A WebM&M commentary discussed a case of a preventable death occurring shortly after a patient with schizophrenia was discharged from a medical hospitalization.