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Understanding and improving the outcomes of psychosis remains a major challenge for clinical research. Obstetric complications (OCs) as a risk factor for schizophrenia (SZ) have been investigated as a potential predictor of outcomes in relation to illness severity and poorer treatment outcome, but there are less reports on first episode psychosis (FEP) patients. We test whether OCs, collected in a cohort of FEP patients, can predict illness course and psychopathology severity after 2 years from the onset. Moreover, we explore whether the SZ-polygenic risk score (PRS) would predict the illness course and whether the interaction between OCS and PRS shows a significant effect. A cohort of 264 FEP patients were assessed with standardized instruments. OCs were recorded using the Lewis–Murray scale in interviews with the patients’ mothers: 30% of them reported at least one OC. Patients with at least one OC were more likely to have a non-remitting course of illness compared to those without OCs (35.3% vs. 16.3%, p = 0.014). No association between SZ-PRS and course of illness nor evidence for a gene–environment interaction was found. In our sample, poor short-term outcomes were associated with OCs, while SZ-PRS was not a prognostic indicator of poor outcomes.