Urine dipstick testing for ketones is widely used when diabetic ketoacidosis (DKA) is suspected in patients with hyperglycaemia. If urinary ketones are positive, patients are referred for further management--often inappropriately, as the test is a poor surrogate for plasma ketones. Plasma beta-hydroxybutyrate (β-OHB) levels>3 mmol/L are diagnostic of DKA, while levels<1 mmol/L are insignificant. To evaluate a hand-held electrochemical (point-of-care testing; POCT) ketone monitor and compare it with the gold-standard manual enzymatic method (MEM) for detection of plasma ketones. In a prospective and comparative study, we evaluated the measurement of β-OHB by means of POCT and the MEM in 61 consecutive samples from patients with suspected DKA at Tygerberg and Karl Bremer hospitals, Cape Town, South Africa. Capillary (for POCT) and plasma samples (for the MEM) were obtained simultaneously and compared for accuracy. Precision was assessed with control samples. The POCT method was precise (coefficient of variation <4.5%), and there was a good correlation between the two methods (r=0.95). Regression analysis showed a proportional bias, with POCT reading higher than the MEM. However, when assessed at the relevant medical decision limits (β-OHB>3 mmol/L and <1 mmol/L), the total allowable error (bias+imprecision) was not exceeded. Patients will therefore still be classified correctly. The POCT method had a sensitivity of 100% and specificity of 89% for DKA (β-OHB>3 mmol/L), while at levels<1 mmol/L sensitivity was 100% and specificity 87.5%. The POCT device provides an accurate and precise result and can be used as an alternative to the MEM in the diagnosis of DKA.