Background: Increased peak postoperative B-type natriuretic peptide (BNP) is associated with increased major adverse cardiovascular events and all-cause mortality after coronary artery bypass graft (CABG) surgery. Whether increased postoperative BNP predicts worse postdischarge physical function (PF) is unknown. We hypothesized that peak postoperative BNP associates with PF assessed up to 2 yr after CABG surgery, even after adjusting for clinical risk factors. including preoperative PF. Methods: This two-institution prospective cohort study included patients undergoing primary CABG surgery with cardiopulmonary bypass. Short Form-36 questionnaires were administered to subjects preoperatively and 6 months, 1 yr, and 2 yr postoperatively. Short Form-36 PF domain scores were calculated using the Short Form-36 norm-based scoring algorithm. Plasma BNP concentrations measured preoperatively and on postoperative days 1-5 were log10 transformed before analysis. To determine whether peak postoperative BNP independently predicts PF scores 6 months through 2 yr after CABG surgery, multivariable longitudinal regression analysis of the postoperative PF scores was performed, adjusting for important clinical risk factors. Results: A total of 845 subjects (mean ± SD age, 65 ± 10 yr) were analyzed. Peak postoperative BNP was significantly associated with postoperative PF (effect estimate for log10 peak BNP, -7.66 PF score points [95% CI, -9.68 to -5.64]; P = <0.0001). After multivariable adjustments, peak postoperative BNP remained independently associated with postoperative PF (effect estimate for log10 peak BNP, -3.06 PF score points [95% CI, -5.15 to -0.97]; P = 0.004). Conclusions: Increased peak postoperative BNP independently associates with worse longer-term PF after primary CABG surgery. Future studies are needed to determine whether medical management targeted toward reducing increased postoperative BNP can improve PF after CABG surgery.