Purpose: Regional muscle-architecture measures are reported widely; however, little is known about the variability of these measurements in the rectus femoris, vastus lateralis, and anterior and lateral vastus intermedius. The aim of this study was to quantify this variability. Methods: Regional muscle thickness, pennation angle (PA), and calculated and extended-field-of-view–derived fascicle length (FL) were quantified in 26 participants using ultrasonography across 51 limbs on 3 occasions. To quantify variability, the typical error of measurement (TEM) was multiplied by 2, and thresholds of 0.2–0.6 (small), 0.6–1.2 (moderate), 1.2–2.0 (large), 2.0–4.0 (very large), and >4.0 (extremely large) were applied. In addition, variability was deemed large when the intraclass correlation coefficient (ICC) was <.67 and coefficient of variation (CV) >10%, moderate when ICC > .67 or CV < 10% (but not both), and small when both ICC > .67 and CV < 10%. Results: Muscle thickness of all muscles and regions had low to moderate variability (ICC = .88–.98, CV = 2.4–9.3%, TEM = 0.15–0.47). PA of the proximal and distal vastus lateralis had low variability (ICC = .85–.96, CV = 3.8–8%) and moderate to large TEM (TEM = 0.42–0.83). PA of the rectus femoris was found to have moderate to very large variability (ICC = .38–.74, CV = 11.4–18.5%, TEM = 0.61–1.29) regardless of region. Extended-field-of-view–derived FL (ICC = .57–.94, CV = 4.1–11.5%, TEM = 0.26–0.88) was superior to calculated FL (ICC = .37–.84, CV = 7.4–17.9%, TEM = 0.44–1.33). Conclusions: Variability of muscle thickness was low in all quadriceps muscles and regions. Only rectus femoris PA and FL measurements were highly variable. The extended-field-of-view technique should be used to assess FL where possible. Inferences based on rectus femoris architecture should be interpreted with caution.