Purpose: Revolumization with deep injections has become increasingly common, even in high-risk areas for intravascular infusion or nerve injury. This study aimed to assess the usefulness of the ultrasonography-guided cannula method for preventing side effects during the injection of polymethylmethacrylate (PMMA) fillers. Real-time ultrasonography was used to monitor the injection of PMMA as a filler in the gluteus for aesthetic purposes. This way, adjacent anatomical structures such as arteries, veins, and nerves could be seen during the whole procedure. Materials and Methods: This study describes the technique used for ultrasound-guided injections of PMMA in the gluteal region of two patients. Patients 1 and 2 were injected with 300 mL and 220 mL of the filler, respectively. Injections were administered intramuscularly and subcutaneously into sites that had been marked before the procedure. While one professional performed the injections, another guided them with real-time ultrasound imaging, using the same equipment for both patients. The location and depth of blood vessels and nerves were determined before the procedure, and the insertion of the cannula was accompanied by ultrasound imaging. Results: The PMMA filler, as well as the cannula, blood vessels, and nerves, was visualized using ultrasound. Some differences were observed between the cases. In the first patient, a small amount of PMMA from a previous procedure could be found (hyperechoic images), while the second one had had no filler injection before. Conclusion: Based on these cases, ultrasonography can be seen as a complementary tool to monitor tissue filler injections, especially in the gluteal region, thus, avoiding possible vascular and nervous injuries. Real-time ultrasound makes the procedure safer, protecting regional structures from lesions. The ultrasonography-guided method succeeded in localizing the cannula, blood vessels, and the sciatic nerve, allowing for safe injection of PPMA filler into a deep gluteal region.