Antipsychotic-induced D2 receptor occupancy values tend to be lower when measured with [123I]IBZM SPECT than with [11C]Raclopride PET. To clarify this issue, D2 receptor occupancy was measured in the same subjects using both techniques. Twenty patients with schizophrenia on monotherapy with risperidone (n = 7; 3–9 mg/d), olanzapine (n = 5; 5–20 mg/d) or clozapine (n = 8; 150–450 mg/d) at stable doses, and ten healthy volunteers (HV) underwent both a [123I]IBZM SPECT and a [11C]Raclopride PET examinations in random order on different days within a week. Patients with schizophrenia were scanned at a fixed interval after last dose administration. Quantification of receptor availability was performed using the most conventional methods from the literature: the tissue ratio derived specific uptake ratios (SUR) were used for SPECT, and simplified reference tissue model (SRTM) derived binding potentials (BPND) for PET. Analysis was performed using both occipital cortex and cerebellum as reference regions for both modalities. Striatal D2 receptor occupancy was measured as the percentage reduction of [123I]IBZM SUR or [11C]Raclopride BPND compared to the population average measured in HV using the same modality. Occupancy values measured by SPECT were lower than those measured with PET, by 12.4% and 13.8% when occipital cortex and cerebellum were used as reference regions. This difference should be taken in consideration when interpreting reported antipsychotic striatal D2 receptor occupancy values from the literature.