BackgroundNonsurgical cosmetic procedures, particularly the use of hyaluronic acid (HA)‐based soft tissue fillers, are becoming increasingly popular. This trend has catalyzed the development of a plethora of HA‐based products differing in product characteristics, thereby catering to an ever‐widening spectrum of aesthetic applications. However, complications rise concomitant with the increasing number of procedures. Among the strategies to manage such adverse events is the enzymatic breakdown with hyaluronidase.ObjectiveTo analyze the response of different HA‐based soft tissue filler materials to hyaluronidase injections.MethodsA total of 11 different HA‐based soft tissue fillers were evaluated using noninvasive ultrasound imaging to assess their behavior in response to hyaluronidase injections. The HA‐based soft tissue fillers were categorized according to their product characteristics into a structuring, volumizing, and lip volumizing group. Standardized injections of 0.2 cc were performed in chicken breast to simulate human tissue. Ultrasound measurements of width, height, and calculated volume were performed immediately after filler injection, 1 h and 24 h following hyaluronidase injection.ResultsRegardless of the soft tissue filler analyzed, the most significant volume reduction occurred within the first h after applying hyaluronidase, with a 64.1% decrease from the initial volume. After 24 h, the total volume reduction reached 81.7%. No statistically significant differences were found when comparing the three groups at each follow‐up time period, except for the height measurement after 1 h. While width was statistically significant in all groups between the investigated follow‐up groups, the volume reduction was only statistically significant in the groups with the highest and second highest G' values (i.e., Group 1—structuring, Group 2—volumizing).ConclusionThe effectiveness of hyaluronidase in dissolving HA‐based fillers is initially independent of product characteristics of HA‐based fillers such as G‐prime, with increased efficacy in fillers with higher G‐prime values, as evidenced by significant volume reductions in such groups.