Injectable poly-l-lactic acid (PLLA) is a new type of biodegradable dermal filler that has been exploited for soft tissue filling. However, there needs to be a more convenient and accurate approach to determine the long-term safety of PLLA filler. The research aimed to examine the long-term safety of PLLA injection into nasolabial folds by high-frequency ultrasonography and select the ultrasonic probes with the most suited frequency. After a 30-month PLLA injection into the deep dermis of the nasolabial fold, individuals were investigated by high-frequency ultrasonography with the 20 MHz and 50 MHz probes. A total of 20 participants with nasolabial fold contour deficiency were enrolled in this investigation. After a 30-month PLLA injection in nasolabial folds, PLLA degraded totally in 16 participants (16/20, 80%), and aberrant echo in the skin was found in 4 patients (4/20, 20%) caused by undegraded PLLA microparticles, PLLA microparticles deposition, fibrous nodules, and granuloma. When analyzing the potentially harmful effects of PLLA injection, the 20-MHz probe is a better choice than the 50-MHz probe because of its lower frequency. Monitoring the degradation state of PLLA and the creation of papules and nodules associated with PLLA injection can be done in a way that is quick, reliable, and does not involve any intrusive procedures by using high-frequency ultrasonography.