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Background Fractional microneedle radiofrequency (FMR) and nonablative 1927-nm fractional thulium fiber laser (TFL) are widely used for skin rejuvenation treatment. Objectives To investigate the efficacy and safety of combined treatment with both devices for wrinkles. Patients and methods Twenty-five patients with wrinkles were enrolled. One side of the face was treated with FMR alone, while the other side was treated with a combination of FMR and TFL. Each treatment consisted of 3 sessions at four-week intervals and patients were followed up 12 weeks after the last treatment. Overall improvement was assessed by patient global assessment (PGA) and investigator global assessment (IGA). Depression scores for the evaluation of wrinkles were objectively assessed by Antera 3D system. Results Both sides of the face led to clinical improvement in both mean PGA and IGA. Combination treatment demonstrated a greater improvement in both mean PGA and IGA compared with FMR alone. In addition, wrinkle grading scales and depression scores showed greater improvement in the combination group than in FMR alone. Conclusion This study demonstrated that FMR and TFL comprise a good combination treatment for the treatment of wrinkles because both treatments have a synergistic effect on wrinkle improvement.