Background: Soft-tissue filler injections performed with a cannula are perceived to be less precise because of the length of the instrument and the blunt tip, which can deviate in any direction. Midfacial needle injections are favored despite the increased risk for intraarterial product placement. The objective of this study was to demonstrate that ultrasound-assisted cannula injections of the midface result in precise, safe, and effective volumization procedures. Methods: Midfacial injections with a 22-G cannula were performed in 188 midfaces of 94 healthy volunteers [86 women; age, 53.05 (9.9) years; 23.63 (2.1) kg/m 2 ] under ultrasound-assisted guidance. Precision (ie, administration of product in the same plane as the location of the cannula tip), safety (ie, rate of adverse events), and aesthetic outcome (rated by the patient and the treating physician) were assessed. Results: In 100% of cases, the product was applied into the desired deep midfacial fat compartment, and the product did not migrate into more superficial layers during the injection process or at any follow-up visit. There was a statistically significant ( P < 0.001) improvement in midfacial volume loss and the aesthetic outcome was rated as very much improved. No adverse events were reported throughout follow-up. Conclusions: Real-time imaging allows for visual feedback during cannula advancement and injection procedures in the midface and can help practitioners achieve safer aesthetic outcomes. It is hoped that practitioners decide to use a cannula more frequently for midfacial volumization, given the results presented in this article. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.