Objective: Patients with traumatic brain injury (TBI) are at moderate risk of GH deficiency (GHD), requiring a diagnostic test with high specificity. The GHRH+arginine (GHRH+ARG) test has been recommended as a reliable alternative to the insulin-tolerance test (ITT) as a standard test with a cutoff level of 9 ng/ml. However, it has recently been questioned for its low specificity in obese subjects, and now BMI-dependent cut-off levels are available. In this study, we compared the ITT and GHRH+ARG test in patients with TBI. Design: A cross-sectional study Methods: We performed an ITT and a GHRH+ARG test in 21 patients with TBI (6 women, 15 men: mean age 40.2 +/- 12.1 years; BMI 30.7 +/- 6.2). The number of patients classified discordantly as GH deficient by the ITT and the GHRH+ARG test with both classical and BMI-dependent cut-off levels was assessed. Results: Using the GHRH+ARG test with the classical cut-off (<= 9 ng/ml), we identified 12 patients as GH deficient who had a normal GH response to ITT (> 3 ng/ml), and one patient as GH sufficient who had a blunted GH response to ITT (discordance rate 61.9%). All patients discordantly classified as GH deficient by the GHRH+ARG test had a BMI of >= 28. With the BMI-dependent cut-offs (4.2, 8.0, and 11.5 ng/ml in obese, overweight, and lean subjects respectively), only 3 of the 21 patients were discordantly classified (discordance rate 14.3%). Conclusions: Our results discourage the use of a cut-off level of 9 ng/ml for the GHRH+ARG test in obese subjects. The diagnostic reliability of this test is improved with the BMI-dependent cut-offs.