The aim of this study was to estimate the effect of index surgical care setting on perioperative costs and readmission rates across 4 common elective general surgery procedures. Facility fees seem to be a driving force behind rising US healthcare costs, and inpatient-based fees are significantly higher than those associated with ambulatory services. Little is known about factors influencing where patients undergo elective surgery. All-payer claims data from the 2014 New York and Florida Healthcare Cost and Utilization Project were used to identify 73,724 individuals undergoing an index hernia repair, primary total or partial thyroidectomy, laparoscopic cholecystectomy, or laparoscopic appendectomy in either the inpatient or ambulatory care setting. Inverse probability of treatment weighting-adjusted gamma generalized linear and logistic regression was employed to compare costs and 30-day readmission between inpatient and ambulatory-based surgery, respectively. Approximately 87% of index surgical cases were performed in the ambulatory setting. Adjusted mean index surgical costs were significantly lower among ambulatory versus inpatient cases for all 4 procedures (P < 0.001 for all). Adjusted odds of experiencing a 30-day readmission after thyroidectomy [odds ratio (OR) 0.70, 95% confidence interval (CI), 0.53-0.93; P = 0.03], hernia repair (OR 0.28, 95% CI, 0.20-0.40; P < 0.001), and laparoscopic cholecystectomy (OR 0.37, 95% CI, 0.32-0.43; P < 0.001) were lower in the ambulatory versus inpatient setting. Readmission rates among ambulatory versus inpatient-based laparoscopic appendectomy were comparable (OR 0.63, 95% CI, 0.31-1.26; P = 0.19). Ambulatory surgery offers significant costs savings and generally superior 30-day outcomes relative to inpatient-based care for appropriately selected patients across 4 common elective general surgery procedures.