We report four cases (2 men and 2 women) of schizophrenia patients resistant to pharmacological treatment, in whom all neuroleptics available in Poland were used without satisfactory effect. Patients were treated in the Department of Psychiatry of Medical University of Lublin between 2008 and 2011. The applied combined therapy consisted of sertindole, 16–20 mg/d and clozapine, 100–600 mg/d. A signiﬁ cant improvement of the mental state was achieved during the ﬁrst two months of gradually introduced treatment. In all patients, a signiﬁ cant reduction of positive and deﬁcit symptom occurred as well as improvement in functioning. Monitoring of the heart did not reveal prolongation of the QT segment or the QTc, and no arrhythmias were observed. The results obtained show that combined treatment with sertindole and clozapine was found to be effective and safe for patients with drug-resistant schizophrenia.