<p>Microfocused ultrasound (MFU) and (MRF) are non-invasive modalities widely used for skin rejuvenation and are often combined with injectables, including neuromodulators and soft tissue fillers. However, large-scale, long-term safety data on such combination therapies are lacking. To address this gap, we conducted a retrospective chart review at two private practice dermatology clinics in South Korea from June 2005 to December 2023. A total of 1,040 patients were included, comprising 515 (49.5%) and 525 (50.5%) patients undergoing MFU and MRF, respectively. Regarding combination therapy, the patients received neuromodulators (76.9%) or dermal filler injections using hyaluronic acid (HA) (17.3%) or poly-L-lactic acid (PLLA) (5.8%) in conjunction with MFU/MRF. Documented adverse events included one case of paradoxical bulging and three cases of eyelid ptosis among those treated with MFU/MRF and neuromodulators (overall incidence: 0.1% and 0.4%, respectively), two cases of surface irregularity among those treated with MFU/MRF and HA fillers (overall incidence: 1.1%), and one case of cheek asymmetry among those treated with MFU/MRF and PLLA injections (overall incidence: 1.7%). No adverse events such as infection, necrosis, burn, filler migration, or unexpected premature loss of filler were reported. While limited by its retrospective design and the inclusion of only two dermatology clinics, which restricts the generalizability of the findings, our study highlights the favorable long-term safety profile of combining MFU and MRF with cosmetic injectables. Our study offers reassurance to clinicians and patients considering these approaches.</p>