Increases in serum triglyceride (TG) levels are associated with clinical response to clozapine treatment. Clozapine is the most efficacious therapy for treatment of refractory schizophrenia, although its use is well recognised to be associated with substantial metabolic dysfunction. Interestingly, there is some evidence that the therapeutic benefit of clozapine is associated with treatment-emergent weight gain and dyslipidaemia, specifically hypertriglyceridaemia. In this prospective observational study, we examine associations between therapeutic response to clozapine in 49 patients with treatment-resistant schizophrenia and lipid dysregulation. An increase in TG levels was strongly predictive of clinical improvement (B=9.33, t=3.56, df=4, p<0.001) and of improvement in positive PANSS scores (B=2.85, t=3.61, df=4, p=0.001) as well as negative PANSS scores (B=1.93, t=2.36, df=4, p=0.02), when controlling for potential confounds of weight gain, change in waist circumference, baseline antipsychotic polypharmacy and serum clozapine levels. This finding suggests that clozapine's therapeutic efficacy is linked to serum lipid changes. Hypertriglyceridaemia as a predictor of clinical response in patients treated with clozapine merits further investigation in order to better elucidate its effect on the pharmacological activity of clozapine.