Vascular endothelial growth factor (VEGF) is implicated in angiogenesis, blood flow, and neuroplasticity, which have previously been shown to contribute to schizophrenia and the mechanisms of action of antipsychotic medication. The aim of the present study was to investigate whether baseline serum VEGF levels predict treatment responses to antipsychotic medication. Drug-free adults with schizophrenia were administered monotherapy with atypical antipsychotic drugs for 6 weeks. Participants’ psychiatric symptoms were assessed using the positive and negative symptom scale (PANSS) before and after treatment. Blood samples for VEGF measurements were collected from 201 participants comprising 83 healthy controls and 118 patients (i.e. only on admission). Baseline VEGF levels in adults with schizophrenia were significantly lower than those in the control group (t = 3.656, df = 199, P < 0.001). In particular, pretreatment VEGF levels were significantly higher in patients responding to drug treatment at follow-up (≥ 50% reduction in initial PANSS total) (t = 4.743, df = 116, P < 0.001). The predictive power of serum VEGF levels was investigated using receiver operating characteristic curves. The area under the curve was 0.774 (95% confidence interval 0.688–0.846); for fixed specificity of 78.8%, the corresponding sensitivity was 63.5%. Results from this preliminary experiment suggest high baseline serum concentrations of VEGF may predict a better response to antipsychotic medications in adults with schizophrenia. Further studies using larger sample sizes are needed to verify the findings.