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The objectives of this study were to describe the onset of hyperketonemia, the number of positive hyperketonemia test results, and the duration of the longest hyperketonemic period during the first 42 d in milk (DIM) in dairy cows. Furthermore, we set out to evaluate test characteristics of single and repeated measurements of β-hydroxybutyric acid (BHBA) during this period to diagnose hyperketonemia. Using an electronic handheld meter, 252 cows from 3 farms were tested twice weekly for hyperketonemia (blood BHBA ≥1.2 mmol/L) during the first 42 DIM, resulting in 12 test results per cow (i.e., in lactation wk 0.5 to 6). Prevalence and incidence of hyperketonemia were calculated for the 12 examination days and the 42-d period, respectively. Test characteristics for the diagnosis of hyperketonemia were calculated for 4 different testing scenarios (testing all cows 1, 2, 3, or 6 times during the first 42 DIM) and 2 different gold-standard definitions (BHBA ≥1.2 mmol/L at least once during the observation period or BHBA ≥1.2 mmol/L at least twice during the observation period). Mean prevalence of hyperketonemia was 11.8%, ranging from 9.6% in lactation wk 0.5 and 2.0 to 14.6% in lactation wk 5.5. In total, 134 cows (53.2%) had at least 1 positive hyperketonemia test result during the whole 42-d period. Of these cows, 46.3% had only 1 positive result. The median first positive hyperketonemia test result was in lactation wk 2.0 [interquartile range (IQR) 1.0-3.5]. Median frequency of positive test results in cows affected by hyperketonemia was 2 positive test results (IQR 1-3). Median duration of the longest hyperketonemic period per cow affected was 1 examination interval (3-4 d; IQR 1-2). Considering a minimum of 1 positive hyperketonemia test result during the first 42 DIM as the gold standard, sensitivity of a single BHBA measurement during this period to diagnose hyperketonemia was 21%. A weekly testing protocol had a sensitivity of 72%. Specificity was 100% in both cases. Considering a minimum of 2 positive hyperketonemia test results as the gold standard, sensitivity and specificity of a single BHBA measurement during the first 42 DIM were 33 and 97%, respectively. A weekly testing protocol provided sensitivity and specificity of 91 and 83%, respectively. We conclude that the risk period for hyperketonemia lasts at least until lactation wk 6, which should be considered when planning hyperketonemia screening programs. Test characteristics of screening protocols depend on testing frequency.