Background Inclusion of the middle hepatic vein (MHV) with a right hepatectomy (RH) in live donor liver transplantation improves venous drainage of the anterior sector of the graft. Its long-term effects on donor left liver (LL) regeneration are not well described. Methods Donors who underwent RH with MHV (MHV+, n = 12) were compared with donors who underwent RH with preservation of the MHV (MHV-, n = 24). Peri-operative complications and volume of the entire liver and individual segments were evaluated at 1 year post-donation. Results There was a trend towards a higher complication rate in the MHV+ group (41% versus 25%), without reaching statistical significance (P = 0.3). Males, high body mass index (BMI) and a smaller residual liver volume (RLV) were predictors for greater LL regeneration. MHV+ donors had impaired regeneration of segment 4 (S4) at 1 year, and compensatory greater left lateral segment regeneration. The absence of venous drainage of S4 (V4) to left hepatic vein (LHV) was a predictor of impaired S4 regeneration. Conclusions Regeneration of S4 is impaired in MHV+ donors. Caution should be taken when considering MHV removal on donors with dominant S4, especially on those with potential increased demand for liver regeneration, such as males, higher BMI and a smaller RLV.