Background: Schizoaffective Disorder (SAD), similarly to schizophrenia, is a potentially chronic mental disorder that negatively affects the functioning of a patient. Various issues in everyday clinical practice often arise from its diagnostic and therapeutic uncertainty. To date, there is a lack of a well-defined therapeutic algorithm used to treat the simultaneously manifesting schizophrenic and affective components. The aim of this study was to compare the therapeutic approaches in schizophrenia and schizoaffective disorders to identify the need of different treatment strategy for these diseases. Methods: In a retrospective study, we evaluated the therapeutic algorithms used in all patients with SAD (n = 99) hospitalized at the Department of Psychiatry, Comenius University in Bratislava, Faculty of Medicine and University Hospital Bratislava throughout the year 2010 and compared them with the therapeutic procedures used in all schizophrenia patients hospitalized in the same year (n = 120). Results: We found similarities between the groups of patients with schizophrenia and SAD in the number, type and length of hospitalizations and general patient management. Differences were identified in terms of the spectrum of used pharmacotherapy. For the treatment of both mental disorders, atypical antipsychotics were used the most. In the treatment of schizophrenia, we found the most frequent use of combined antipsychotic therapy, meaning oral and long-acting injectable forms. Patients with SAD mostly received antipsychotic monotherapy, but its complex effects were supplemented with other psychotropic drugs, mostly mood-stabilizers and anxiolytics. Conclusion: The results of our study show similarities between schizophrenia and SAD in terms of health care utilization, despite the fact that SAD is generally considered to be a “milder” disorder. On the other hand, this study indicates differences in the spectrum of pharmacotherapy used.