Context: It has been hypothesized that increased plasma bile acids (BAs) contribute to metabolic improvements after Roux-en-Y gastric bypass (RYGB) surgery by the G protein-coupled receptor TGR5-mediated effects on glucagon-like peptide-1 secretion and thyroid hormones. Objective: The objective of this study was to evaluate the importance of bariatric surgery-induced alterations in BA physiology on factors that regulate glucose homeostasis (insulin secretion and sensitivity) and energy metabolism (resting energy expenditure and thyroid hormone axis). Design, Participants, Intervention, and Main Outcome Measure: Eighteen extremely obese subjects were studied before and after 20% weight loss, induced by either laparoscopic adjustable gastric banding (LAGB) (n = 10) or RYGB surgery (n = 8). Results: Plasma BAs more than doubled after RYGB [fasting: 1.08 (0.26-1.42) to 2.28 (1.59-3.28) μmol/L, P = .03; postprandial: 2.46 ± 1.59 to 6.00 ±2.75 μmol/L, P = .01] but were either lower or did not change after LAGB [fasting: 1.80 (1.49-2.19) to 0.92 (0.73-1.15) μmol/L, P = .02; postprandial: 3.71 ± 2.61 to 2.82 ± 1.75 μmol/L, P = .14]. Skeletal muscle expression of TGR5 targets, Kir6.2 and cyclooxygenase IV, increased after RYGB but not LAGB. Surgery-induced changes in BAs were associated with increased peak postprandial plasma glucagon-like peptide-1 (r2 = 0.509, P = .001) and decreased serum TSH (r 2 = 0.562, P < .001) but did not correlate with the change in insulin response to a meal (r2 = 0.013, P = .658), insulin sensitivity (assessed as insulin stimulated glucose disposal during a hyperinsulinemic-euglycemic clamp procedure) (r2 = 0.001, P = .995), or resting energy expenditure (r2 = 0.004, P = .807). Conclusions: Compared with LAGB, RYGB increases circulating BAs and TGR5 signaling, but this increase in BAs is not a significant predictor of changes in glucose homeostasis or energy metabolism.