OBJECTIVES: The primary objective compared antipsychotic non-adherence rates of outpatients with schizophrenia or schizoaffective disorder as assessed by electronic monitoring vs. prescriber ratings. Secondary objectives evaluated the relationship between electronically-determined antipsychotic adherence with (1) various baseline patient characteristics and (2) prospectively assessed symptom severity, quality of life (QoL) and cognition. METHODS: Adult outpatients with schizophrenia or schizoaffective DSM-IV diagnosis, taking a single oral antipsychotic, and who signed informed consent were eligible. Adherence was measured via electronic-monitored medication vial caps, prescriber report, patient self-report and research assistant report, at baseline and monthly for up to six-months, as were symptom severity (PANSS) and QoL (SQLS, LOF, PSP). Patients were non-adherent if adherence was <70% for two or more months during the six-month study. A single cognition assessment (BACS) was performed. RESULTS: Sixty-one patients (mean age 44.3„b9.1 years, 51% female, illness duration 21.2 „b 10.7 years) were included. Antipsychotic non-adherence detection was significantly higher with electronic monitoring (57%) vs. prescriber assessment (7%; p<0.0001, N=60) and vs. patient self-assessment (5%; p<0.0001), but was not different from research assistant assessment (54%; p<0.67). While the total number of patients classified as adherent and non-adherent by research assistants and electronic monitoring were similar, disagreement in assignment occurred in 36% of cases. Poorer mean adherence was associated with baseline characteristics of less than high school education (p<0.0001), non-Caucasian race (p=0.001), and more severe symptoms (p=0.001). Lower mean adherence rates were also associated with worse mean six-month symptom (PANSS total; p<0.002) and lower functioning on one of three QoL scales (SQLS;p<0.03) ratings. No relationship was found between adherence and cognition. CONCLUSION: In patients with schizophrenia and schizoaffective disorder, non-adherence is significantly underestimated/underreported by prescribers and patients. Results suggest non-adherence with antipsychotic medication therapy is associated with worse symptoms, poorer QoL, less than high school education and non-Caucasian race.