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Supplemental Digital Content is available in the text., Background: Hyaluronic acid (HA) fillers for volume augmentation in the anteromedial malar region of Asians have been popular for many years. However, studies on their long-term effectiveness are lacking. This study aimed to evaluate the effectiveness and safety of HA fillers injected into the anteromedial malar region for volume augmentation for up to 52 weeks. Methods: Each anteromedial malar region of the subjects was treated with YVOIRE Contour (YVOC) in one side and Restylane Sub-Q (RESS) in the other and followed up at weeks 2, 14, 26, and 52. The volume using the mid-face aesthetic scale (MFAS) ranging from 0 (full) to 4 (very severely sunken) and the subject’s satisfaction and adverse events were evaluated. Results: Total 83 subjects were randomized and treated with YVOC and RESS. The LS means (standard error) of MFAS score in the YVOC and RESS groups were both 2.56 (0.05) at baseline, 1.32 (0.07) and 1.39 (0.07) at week 26, and 1.84 (0.10) and 1.89 (0.10) at week 52, respectively. The difference in the LS mean of MFAS score between the groups at week 26 was 0.07 (95% confidence interval, 0.01–0.12), showing the non-inferiority of YVOC to RESS. About 70% of subjects were still satisfied with the results at week 52. No specific safety concern was detected. Conclusions: The HA fillers injected for the anteromedial malar augmentation maintained the volume well for up to 52 weeks. Additionally, both YVOC and RESS show similar effectiveness and safety profiles.