Clozapine has superior efficacy for treating patients with schizophrenia. Its discontinuation could have detrimental consequences. We attempted to identify the clinical parameters that could predict clozapine discontinuation in patients diagnosed as having schizophrenia by conducting a retrospective analysis of all of those who started on clozapine treatment during their hospitalization in our institution between 2002 and 2008 (n=100). Demographic and clinical parameters were analyzed and compared between the 58 patients who continued and the 42 who discontinued clozapine treatment during a follow-up period of 8.1 years. Twenty of the latter patients (47.6%) discontinued clozapine because of nonadherence and 11 (26.2%) because of side effects. Thirty-three of them (78.6%) stopped taking clozapine during the first year of treatment. The duration of clozapine use correlated significantly with the time to readmission (P<0.001). The decrease in number of suicide attempts was higher in those who continued clozapine treatment compared with those who discontinued it (P=0.02). Predictors for drug discontinuation were old age at clozapine initiation and comorbid substance abuse. These findings indicate that patients with schizophrenia with those risk factors need special incentives to be compliant during the first year of clozapine treatment to minimize the negative sequelae of clozapine discontinuation.