Aims: To determine the cost and performance of a Danish risk score, fasting plasma glucose (FPG), and HbA1c as single screening tests and in combination with targeted screening. Subjects and methods: In the Inter99 study, 12 934 inhabitants of Copenhagen County were invited to participate. All participants underwent anthropometric measurements, blood samples, and a 75-g standardized oral glucose tolerance test [N = 6784 (52.5%)]. Results: Of the 6117 individuals included in the analysis, 252 (4.1%) had previously undiagnosed diabetes. As a stand-alone test, the FPG had the highest performance expressed by a significantly higher area under the receiver-operating curve [0.89; 95% confidence interval (CI) 0.86, 0.99] compared with the Danish risk score (0.78; 95% CI 0.76, 0.81) and HbA1c (0.76; 95% CI 0.72, 0.80). Targeted screening where the initial test was a risk score reduced the FPG measurements by 72% (100% vs. 27.8%). Using FPG in population-based screening, the cost per newly diagnosed diabetic individual was 583 euro compared with 270 euro if screened by questionnaire followed by FPG. The sensitivity and specificity were 78.6% and 87.7% for FPG, and 61.5% and 89.2% for the combination of the questionnaire and FPG, respectively. Conclusions: The performance of FPG was superior to a questionnaire and HbA1c used as single tests. However taking into account workload, the burden on the population and the cost per identified person with undiagnosed diabetes, targeted screening using a questionnaire followed by FPG appears to be the strategy of choice.