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The chronic clinical course of schizophrenia, resistance to treatment, drug side effects, different responses of negative and cognitive symptom clusters to anti-psychotic medications with different receptor profiles may require combination therapy and thus antipsychotic poly-pharmacy. Although the frequency of poly-pharmacy may vary between 46% to 70% in different countries and years, most studies report antipsychotic poly-pharmacy in nearly half of the patients. Anti-psychotic poly-pharmacy was reported between 38.2 – 64.7% of patients with schizophrenia – spectrum of disorders in Turkey. The aim of this report to present the data* about the drug interaction risks in the patients with schizophrenia spectrum disorders (schizophrenia or schizo-affective disorder) receiving antipsychotic treatment in a provincial area of Turkey reşecting real world conditions. As far as we know, no study was undertaken to investigate the risk of drug interactions that these patients may experience in Turkey. The baseline pharmacotherapy data of a prospective naturalistic study (Project Number: 2008TPF029) supported by the Committee of Scientific Research Projects of Pamukkale University were used in this report. The study sample consisted of 240 patients with schizophrenia spectrum disorders. Co-administration of antipsychotics and other psychotropic drugs for at least 4 weeks were recorded as poly-pharmacy. As individual treatment regiments all used medications for each patient, drug-drug interaction risks were evaluated via the internet site http://www.drugs.com/ and; interaction information for healthcare professionals were used. We found that 56.7% of our patients were under antipsychotic monotherapy, of 35.8% were treated with two antipsychotic medications. A total of 172 (71.7%) patients were taking medications with a risk of interaction, with 417 total drug interaction risks. 87.8% of the interaction risks were at a moderate level. Approximately one quarter of the patients (24.4%) were using medications with a major interaction risk. The majority of major interaction risks were QT prolongation (83.3%) risk, and 9.5% were risk of hypotension – serious bradycardia, 7.2% were the risk of changes in blood drug levels. Among the drug interactions risks related to QT prolongation, 26.2% had a warning of contra-indication. The medications with a risk of QT prolongation were ziprasidone, quetiapine, citalopram / escitalopram, clozapine and haloperidol. All of the major interactions that were related with drug blood levels consisted of quetiapine – carbamazepine interaction. The present report suggested that an important percentage of patients are exposed to drug – drug interactions with ever increasing use of multiple medications in schizophrenia spectrum disorders, and among these interactions, most major risks were cardiovascular risks, and especially QT prolongation. Prospective studies with larger numbers of patients are needed in this topic.