The relationship between antipsychotic use and cardiovascular morbidity and mortality is controversial. There is a lack of long-term prospective studies investigating changes in cardiometabolic risk in patients treated with antipsychotic drugs. We report data from a 4-year prospective study. Patients (89) underwent detailed metabolic and cardiovascular risk assessment at 4-years which included anthropometric assessment, blood pressure, lipid profile, and an oral glucose tolerance test. We used the homeostatic model assessment to determine insulin resistance, and calculated 10-year cardiovascular risk scores. Mean age of subjects was 44.7 (±11.5) years, and 52% were male. The prevalence of type 2 diabetes was 8%, and 38.4% fulfilled diagnostic criteria for the metabolic syndrome. With the exception of increased central adiposity over the 4-year follow-up period (p < 0.001), other cardiometabolic parameters were generally unchanged. There was a high prevalence of dyslipidaemia, but only 16.9% were prescribed lipid-lowering treatment. Commencing lipid-lowering therapy was associated with a reduction in cardiovascular risk score (OR 7.9, 95% CI = 1.3 to 48.7; p = 0.02). Patients established on longer-term antipsychotic treatment show less dramatic metabolic changes than those occurring in the early stages of treatment, but have a high burden of cardiovascular risk. Lipid-lowering therapy is associated with a significant reduction in cardiovascular risk.