The choice of general (GA) versus local anesthesia (LA) in open inguinal hernia repair (OIHR) has a substantial financial impact and may influence clinical outcomes. Our study compares postoperative quality of life (QOL) in patients undergoing OIHR under LA versus GA. A cooperative prospective study from centers in 10 countries was performed through the International Hernia Mesh Registry from 2007 to 2012. QOL was compared at one, six, 12, and 24 months for LA versus GA with univariate and multivariate analysis controlling for known confounding variables. Of 1128 patients who underwent OIHR, 585(52%) used GA and 533(48%) used LA. Most were male (92%) with unilateral (94%), primary (91%) repairs with a mean age 57 ± 16 years. There was no difference (P > 0.05) in age, gender, operative time, mesh size, length of stay, infection, recurrence, reoperation, or death. Multivariate analysis demonstrated significant QOL differences between groups: GA had higher odds of discomfort at one and six months [odds ratio (OR) 3.3, 2.0], movement limitation at one and six months (OR 3.5, 2.8), and mesh sensation at one and 12 months (OR 2.9, 1.8). Overall, patients undergoing OIHR under LA had improved postoperative QOL in the short and long term compared with GA.