Application of endoscopic vein harvest (EVH) in infrainguinal bypass surgery generated mixed results. The purpose of this study was to compare outcomes between endoscopic vein harvest and open vein harvest (OVH) in femoral-to-popliteal artery bypass (FPB). Case series analysis that involved all patients undergoing femoral-to-popliteal artery bypass with single-segment great saphenous vein between January 2012 and December 2017. There were 170 femoral-to-popliteal artery bypasses performed in 168 patients who met the inclusion criteria; 25 (14.7%) in EVH group and 145 (85.3%) in OVH group. Chronic limb-threatening ischemia was an indication for surgery in 60% of EVH patients and 79% of OVH patients (15/25; 60% EVH vs 114/145; 79% OVH; p = .08). Mean follow-up was significantly longer for EVH group (65.71 months EVH vs 45.32 months OVH; p = .003). EVH group had a lower wound complication rate (4/25; 16% EVH vs 45/145; 31% OVH; p = .336), especially at the harvest incision site, despite higher rate of obesity amongst EVH patients (15/25; 60% EVH vs 35/145; 24% OVH; p < .001). The reintervention rate was higher in EVH group (10/25; 40% EVH vs 42/145; 29% OVH; p = .38). At 5 years, primary (69.1% EVH vs 67.0% OVH; p = .85), primary assisted (87.6% EVH vs 73.5% OVH; p = .18), and secondary patency rates (87.3% EVH vs 76.7% OVH; p = .25) did not demonstrate significant differences between the groups. Endoscopic vein harvest for femoral-to-popliteal artery bypass decreased the rate and severity of wound complications, but this difference was statistically insignificant. Obese patients are more suitable for endoscopic vein harvest, with relatively lower chances of developing wound infections. Despite the higher rate of reinterventions, endoscopic vein harvest patency rates were in line with those for the open vein harvest group in up to 5 years of follow-up.