BACKGROUND: The combination of calcium hydroxylapatite (CaHA) and hyaluronic acid fillers (CPM-HA, cohesive polydensified matrix-based hyaluronic acid fillers, Belotero OBJECTIVE: The objective of the present study is to assess the safety of premixing CaHA and CPM-HA fillers for rejuvenation purposes or as an aesthetic harmonization treatment. METHODS: This retrospective study presents the clinical experience of two expert injectors who consistently used premixed CaHA and CPM-HA fillers for aesthetic treatments between March 2018 and December 2023. The premixed hybrid formulation was standardized and administered following a published protocol. A total of 2112 patients were treated, with meticulous follow-up over a minimum of one year. RESULTS: In the 2112 patients treated, only 5 minor adverse events (0.24%) were reported. The adverse events consisted of 4 non-inflammatory nodules of which 2 completely resolved with hyaluronidase, and 1 case of transient edema. Secondary findings consist of the treated areas, type of CPM-HA used and mixing ratios that were applied. CONCLUSION: The results from the current retrospective study, with the largest published cohort so far, are consistent with prior publications and strongly support a good safety profile of the CaHA:CPM-HA hybrid blend. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .