OBJECTIVES: In the absence of data on the economic impact of the metabolic syndrome amongst South Africans, this study aims to investigate the direct cost of treatment associated with the syndrome using data from a South African Pharmacy Benefit Management company (PBM).  METHODS: A non-experimental, retrospective quantitative drug utilisation review was performed using prescription claims data. Data for a 4-year period (January 1, 2005 to December 31, 2008) were analysed. The direct costs of medicine treatment were computed by the addition of the medical scheme contribution and the patient levy. All costs were respectively expressed in 2005, 2006, 2007 and 2008 $U.S.   RESULTS: Prescription claims data for a total of 10,567 patients in 2005; 12,123 in 2006; 12,769 in 2007 and 13,201 in 2008 with a diagnosis of metabolic syndrome were included in the study. The total direct cost of medicine treatment for these patients accounted for $7,921,831.10 in 2005, compared to $9,290,773.29 in 2006, $9,780,931.85 in 2007 and $8,515,349.53 in 2008. These costs represented 2.76% (N=$287,538,709.70) of all claims during 2005, compared to 3.18% (N=$292,314,629.60) of claims in 2006, 3.58% (N=$273,086,935.30) in 2007, and 3.87% (N=$220,144,319.80) in 2008. Private insurers contributed 90.91% (N=$7,921,831.10) towards the treatment of patients with metabolic syndrome in 2005, compared to 89.92% (N=$9,290,773.29) during 2006, 89.50% (N=$9,780,931.85) in 2007 and 87.17% (N=$8,515,349.53) in 2008. Patients paid on average $68.15±106.18 (median $17.59) out-of-pocket for levies for 2005, compared to $77.21±110.54 (median $35.30) during 2006, $80.42±98.43 (median $49.15) in 2007 and $82.76±96.64 (median $52.66) in 2008.  CONCLUSIONS: Results show that the costs associated with the metabolic syndrome contributes significantly towards the annual expenditure of the South African PBM. Private insurers carry most of this burden, although out-of-pocket expenses for patients show an increasing trend.