Objectives: To evaluate the accuracy of ultrasound (US)-guided and palpation-guided knee injections by an experienced and a less-experienced clinician with use of a superolateral approach. Design: Single-blinded, prospective study. Setting: Academic institution procedural skills laboratory. Participants: Twenty cadaveric knee specimens without trauma, surgery, or major deformity. Intervention: US-guided and palpation-guided knee injections of colored liquid latex were performed in each specimen by an experienced and a less-experienced clinician with use of a superolateral approach. The order of injections was randomized. The specimens were subsequently dissected by a blinded investigator and assessed for accuracy. Main Outcomes: Accuracy was divided into 3 categories: (1) accurate (all of the injectate was within the joint), (2) partially accurate (some of the injectate was within the joint and some was within the periarticular tissues), and (3) inaccurate (none of the injectate was within the joint). The accuracy rates were calculated for each clinician and guidance method. Results: US-guided knee injections that used a superolateral approach were 100% accurate for both clinicians. Palpation-guided knee injections that used a superolateral approach were significantly influenced by experience, with the less-experienced investigator demonstrating an accuracy rate of 55% (95% confidence interval = 34%-74%) and the more experienced investigator demonstrating an accuracy rate of 100% (95% confidence interval = 81%-100%). Conclusions: US-guided knee injections that use a superolateral approach are very accurate in a cadaveric model, whereas the accuracy of palpation-guided knee injections that use the same approach is variable and appears to be significantly influenced by clinician experience. These findings suggest that US guidance should be considered when one performs knee injections with a superolateral approach that require a high degree of accuracy.