Venous thromboembolism (VTE) is the most frequent 30-day complication in patients with morbid obesity undergoing bariatric surgery. Therefore, there is a need for optimized low molecular weight heparin (LMWH) thromboprophylaxis dosing strategies in order to avoid VTE-associated morbidity and mortality in this patient population.The primary goal was to evaluate if a pre-specified enoxaparin dosing regimen in patients undergoing bariatric surgery reaches anti-factor Xa (aFXa) levels in the defined target range (0.2-0.4 U/ml). Second, we aimed to identify biometric and laboratory parameters that might influence the aFXa value.A prospective database of 236 patients with obesity who received thromboprophylaxis with enoxaparin was established. These patients were divided into two weight-adjusted groups (group 1 < 150 kg, group 2 ≥ 150 kg). Enoxaparin was administered twice daily; dosing was determined by weight (group 1, 2 × 40 mg/day; group 2, 2 × 60 mg/day). In both groups, the peak aFXa serum level was evaluated 3 days after initiating the thromboprophylaxis.In group 1 (body mass index (BMI) 42.94 ± 6.84 kg/m, weight of 121.7 ± 17.49 kg), seventy-one of the included 124 patients (57.25%) reached the aFXa target range of 0.2 to 0.4 U/m. In group 2 (BMI 63.21 ± 10.05 kg/m, weight of 191.66 ± 33.37 kg), 68 of 112 (60.71%) patients scored prophylactic aFXa range. Multiple regression of the biometric and laboratory parameters showed significance for weight, waist-to-hip ratio, glomerular filtration rate (GFR), creatinine, and HbA1c exclusively in group 1. There was no case of VTE within 3 months after surgery and no case of severe perioperative bleeding in those patients who underwent surgery.Measurement of the aFXa level helps to define the real prophylactic thromboprophylaxis status in patients with obesity, especially in those with a weight above 150 kg. In patients at risk, the measurement of aFXa should be considered in routine clinical practice.