Living liver donation is a successful treatment for patients with end-stage liver disease. Most adults are provided with a right lobe graft to ensure a generous recipient liver volume. Some centers are re-exploring the use of smaller left lobe grafts to potentially reduce the donor risk. However, the evidence showing that the donor risk is lower with left lobe donation is inconsistent, and most previous studies have been limited by potential learning curve effects, small sample sizes, or poorly matched comparison groups. To address these deficiencies, we conducted a case-control study. Forty-five consecutive patients who underwent left hepatectomy (LH; n ΒΌ 4) or left lateral segmentectomy (LLS; n ΒΌ 41) were compared with matched controls who underwent right hepatectomy (RH) or extended right hepatectomy (ERH). The overall complication rates of the 3 groups were similar (31%-37%). There were no grade 4 or 5 complications. There were more grade 3 complications for the RH patients (13.3%) and the ERH patients (15.6%) versus the LH/LLS patients (2.2%). The extent of the liver resection significantly correlated with the peak international normalized ratio (INR), the days to INR normalization, and the peak bilirubin level. A univariate analysis demonstrated that hepatectomy, the spared volume percentage, and the peak bilirubin level were strongly associated with grade 3 complications. A higher peak bilirubin level, which correlated with a lower residual liver volume, was associated with grade 3 complications in a multivariate analysis (P ΒΌ 0.005). RH and grade 3 complications were associated with an increased length of stay (>7 days) in a multivariate analysis. In conclusion, this analysis demonstrates a significant correlation between the residual liver volume and liver dysfunction, serious adverse postoperative events, and longer hospital stays. Donor safety should be the first priority of all living liver donor programs. We propose that the surgical procedure removing the smallest amount of the liver required to provide adequate recipient graft function should become the standard of care for living liver donation.