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To test the validity and reliability of the Diagnostic Interview for Genetic Studies (DIGS) in patients with mental illness in Croatia.Following translation, back-translation, and pilot testing, the Croatian version of DIGS (CRO-DIGS) was administered to a total of 150 inpatients and outpatients diagnosed at the Clinical Hospital in Split with bipolar and major depressive disorder (n=56), schizophrenia and schizoaffective disorder (n=62), and alcohol dependence or use disorders (n=32). Initial testing was performed independently by one interviewer and one observer blinded to the diagnosis, and a retest was performed after 8 weeks by a third examiner.The validity of CRO-DIGS was high (κ=0.916), with an excellent inter-rater (κ=0.824) reliability, especially for bipolar disorder (κ=0.956). Following an 8 week test–retest interval, the reliability for all diagnoses was found to be excellent (κ=0.843).Our study has shown excellent validity and reliability of the Croatian version of DIGS, making it a promising instrument to assess mental illness of patients. The development of a valid and reliable diagnostic tool such as the CRO-DIGS will considerably advance the scientific communities’ ability to carry out genetic studies of psychiatric illness in the region.