Clozapine is an atypical dibenzodiazepine antipsychotic drug, which was approved widely for resistant cases of schizophrenia, but as yet not for resistant bipolar affective disorder (BAD), despite some researchers suggesting its use in the long-term treatment of resistant bipolar affective disorder. This paper presents a prospective monitored evidence over a five-year period for this claim, using ail previously used outcome measures in the same setting in Saudi BAD patients. Eleven patients consecutively admitted with chronic BAD to King Khalid University Hospital (KKUH) were tried on at least two mood stabilizers, separately or in combination, one of them lithium for at least two years. Improvement outcome was assessed using the Brief Psychiatric Rating Scale (BPRS), the Clinical Global Impression (CGI), the Quality of Life Scale (QLS) and the Extrapyramidal Symptom Rating Scale (ESRS). Also work status, suicidality, the number of admissions; the number of attendances to accident and emergency (A/E) rooms and the number of relapses were measured before and after treatment. All above measures showed statistically significant improvement ail through the period of the study except the QLS measure. This report, in spite of the small number of patients studied, presents reasonable evidence for the long-term efficacy of Clozapine monotherapy in chronic resistant BAD patients.