Objective: With the pandemic of obesity the identification of individuals with hypercortisolism gets more difficult. We analyzed the performance of the 1 mg dexamethasone suppression test (DST) in patients with obesity in a clinical setting. Design and method: We conducted a prospective cohort study in patients with obesity (MOS, NCT00770276). Patients presented in our outpatient department for metabolic and cardiovascular evaluation. After obtaining medical history patients were analysed for anthropometry, metabolism, and cardiovascular risk factors. For evaluation of hypercortisolism we performed a 1 mg dexamethasone-suppression test (DST) in all subjects as screening. In case of insufficient suppression of cortisol (>50nmol/l) further diagnostic assessment was performed: repeat DST, salivary midnight cortisol (SMC) and/or 24 h urine free cortisol (UFC). Medication was assessed for drugs with possibly interfering effects on DST and hypothalamic-pituitary-adrenal axis (e.g. CYP3A4 inducers, estrogen therapy, antidepressants and opiates). Results: A total of 278 patients with a mean age of 42.3years with a female predominance (68.8% women) were screened by DST. Anthropometrical data revealed a mean BMI of 47.9 ± 8.4 kg/m2 and a waist circumference of 137 ± 17.6 cm representing truncal obesity. Insufficient suppression of cortisol after DST was found in 24 patients (8.6%). In 2 patients hypercortisolism was confirmed by UFC. The specificity for DST was calculated with 92.0%. 45.0% of the cohort received confounding medication. Only CYP 3A4 inducers (n = 22, 7.9%) and estrogen therapy (n = 17, 6.1%) were significantly associated with pathological DST. After elimination of all patients with interfering medication specificity slightly increased to 94.9%. Regression analysis revealed no interrelation between DST and anthropometry. Conclusions: In obese patients presenting for bariatric therapy in a tertiary care center we found low prevalence of hypercortisolism (0.7 or < 1.8%). Specificity of DST in this cohort typically screened for hypercortisolism was 92.0% (<51nmol/l), which represents adequate performance. After elimination of interfering medication (CYP3A4 inducers and estrogen therapy) specificity increased only slightly. Furthermore, regression-analysis revealed no association with anthropometrical data, even though we studied patients with extreme measures. In summary DST is an adequate test for screening for hypercortisolism in a real clinical setting.