OBJECTIVES: Treatment optimization for patients with schizophrenia remains a challenge, and it is often difficult to determine whether augmenting the current medication or switching to another will better benefit a patient. This post hoc analysis compares outcome measures between patients whose antipsychotic medication was either augmented or switched. METHODS: Adult outpatients receiving oral antipsychotic treatment for schizophrenia were assessed during a 12-month, multi-country, observational study (F1D-AY-B033). Clinical and functional outcomes were assessed at the time of first treatment switch/augmentation (0–14 days preceding change) and compared between patients undergoing medication augmentation or switching. Due to low numbers of patients with such data, interpretation of findings is based on effect size (ES).  RESULTS: Data at the time of medication change were available for 87 patients (34 augmented, 53 switched). The primary reason for treatment change in both groups was inadequate response, but lack of adherence was more prevalent in the switched group (26.4% versus 8.8%). Although changes in clinical severity from study initiation to medication change were similar (per the Clinical Global Impressions—Severity scale), patients’ physical well being, as measured by physical component scores of the 12-item Short Form Health Survey (SF-12), improved in the augmented group but worsened in the switched group (augmented: +7.71±11.98, switched: –1.87±10.98, ES=0.85). Similarly, mental health state improved in the augmented group but declined in the switched group, as indicated by SF-12 mental health component scores (augmented: +2.41±13.64, switched: –1.08±9.98, ES=0.314). CONCLUSIONS: Patient's worsening or lack of meaningful improvement may prompt clinicians to switch antipsychotic medications, whereas, when a patient shows improvement, clinicians appear more likely to try to bolster the improvement through augmentation with another antipsychotic medication. Current findings are consistent with physicians' stated reasons for augmenting versus switching antipsychotics in the treatment of schizophrenia. Confirmation of these findings requires further research.