Objectives: To measure changes in the composition of serum bile acids (BA) and the expression of Takeda G-protein-coupled receptor 5 (TGR5) acutely after bariatric surgery or caloric restriction. Summary Background Data: Metabolic improvement after bariatric surgery occurs before substantial weight loss. BA are important metabolic regulators acting through the farnesoid X receptor and TGR5 receptor. The acute effects of surgery on BA and the TGR5 receptor in subcutaneous white adipose tissue (WAT) are unknown. Methods: A total of 27 obese patients with type 2 diabetes mellitus were randomized to Roux-en-Y gastric bypass (RYGB) or to hypocaloric diet (HC diet) restriction (NCT 1882036). A cohort of obese patients with and without type 2 diabetes mellitus undergoing vertical sleeve gastrectomy was also recruited (n = 12) as a comparison. Results: After vertical sleeve gastrectomy, the level of BA increased [total: 1.17±1.56mmol/L to 4.42±3.92mmol/L (P = 0.005); conjugated BA levels increased from 0.99±1.42mmol/L to 3.59±3.70mmol/L (P = 0.01) and unconjugated BA levels increased from 0.18±0.24mmol/L to 0.83±0.70mmol/L (P = 0.009)]. With RYGB, there was a trend toward increased BA [total: 1.37±0.97mmol/L to 3.26±3.01mmol/L (P = 0.07); conjugated: 1.06±0.81mmol/L to 2.99±3.02mmol/L (P = 0.06)]. After HC diet, the level of unconjugated BA decreased [0.92±0.55mmol/L to 0.32 ± 0.43mmol/L (P = 0.05)]. The level ofWAT TGR5 gene expression decreased after surgery, but not in HC diet. Protein levels did not change. Conclusions: The levels of serum BA increase after bariatric surgery independently from caloric restriction, whereas the level ofWAT TGR5 protein is unaffected.