Obese patients have lower plasma concentrations of the cardiac natriuretic peptides (NPs) than their age- and sex-matched counterparts. This may reflect lower production and/or increased peptide clearance. It is unclear whether NP bioactivity is affected by obesity. We studied the effects of obesity on B-type natriuretic peptide (BNP) clearance and bioactivity by comparing results from standardized intravenous infusions of BNP administered 2 weeks before and 6 months after bariatric surgery in 12 consecutive patients with morbid obesity (body mass index, BMI > 35 kg/m2). Anthropometric, clinical, neurohormonal, renal, and echocardiographic variables were obtained pre- and postsurgery. Pre- vs postsurgery calculated intrainfusion peptide clearances were compared. BMI (44.3 ± 5.0 vs 33.9 ± 5.2 kg/m2, P < 0.001) and waist circumference (130.3 ± 11.9 vs 107.5 ± 14.7 cm, P < 0.001) decreased substantially after bariatric surgery. Calculated plasma clearance of BNP was reduced (approximately 30%) after surgery. Though not controlled for, sodium intake was presumably lower after bariatric surgery. Despite this, preinfusion endogenous plasma NP concentrations did not significantly differ between pre- and postsurgery studies. The ratio of plasma N-terminal (NT)-proBNP to 24 h urine sodium excretion was higher postsurgery (P = 0.046; with similar nonsignificant findings for BNP, atrial NP (ANP) and NT-proANP), indicating increased circulating NPs for a given sodium status. Mean plasma NP concentrations for given calculated end-systolic wall stress and cardiac filling pressures (as assessed by echocardiographic E/e') rose slightly, but not significantly postsurgery. Second messenger, hemodynamic, renal, and neurohormonal responses to BNP were not altered between studies. Obesity is associated with increased clearance, but preserved bioactivity, of BNP.