["\nAbstract\nWe analysed the importance of systemic and peripheral arteriovenous O2 difference (\n\n difference and a‐vfO2 difference, respectively) and O2 extraction fraction for maximal oxygen uptake (\n\n). Fick law of diffusion and the Piiper and Scheid model were applied to investigate whether diffusion versus perfusion limitations vary with \n\n. Articles (n = 17) publishing individual data (n = 154) on \n\n, maximal cardiac output (\n\n; indicator‐dilution or the Fick method), \n\n difference (catheters or the Fick equation) and systemic O2 extraction fraction were identified. For the peripheral responses, group‐mean data (articles: n = 27; subjects: n = 234) on leg blood flow (LBF; thermodilution), a‐vfO2 difference and O2 extraction fraction (arterial and femoral venous catheters) were obtained. \n\n and two‐LBF increased linearly by 4.9‐6.0 L · min–1 per 1 L · min–1 increase in \n\n (R2 = .73 and R2 = .67, respectively; both P < .001). The \n\n difference increased from 118‐168 mL · L–1 from a \n\n of 2‐4.5 L · min–1 followed by a reduction (second‐order polynomial: R2 = .27). After accounting for a hypoxemia‐induced decrease in arterial O2 content with increasing \n\n (R2 = .17; P < .001), systemic O2 extraction fraction increased up to ~90% (\n\n: 4.5 L · min–1) with no further change (exponential decay model: R2 = .42). Likewise, leg O2 extraction fraction increased with \n\n to approach a maximal value of ~90‐95% (R2 = .83). Muscle O2 diffusing capacity and the equilibration index Y increased linearly with \n\n (R2 = .77 and R2 = .31, respectively; both P < .01), reflecting decreasing O2 diffusional limitations and accentuating O2 delivery limitations. In conclusion, although O2 delivery is the main limiting factor to \n\n, enhanced O2 extraction fraction (≥90%) contributes to the remarkably high \n\n in endurance‐trained individuals.\n", "Acta Physiologica, Volume 230, Issue 2, October 2020. "]