BACKGROUND: Recent preclinical studies have demonstrated the potential efficacy of stem cell exosomes in the treatment of hair loss. However, there is a paucity of clinical studies investigating the application of exosomes for this purpose. This case series presents three patients treated with exosomes for acquired trichorrhexis nodosa (ATN), a condition characterized by hair shaft abnormalities and breakage. OBJECTIVES: This study aims to evaluate the effectiveness and safety of utilizing mesenchymal stem cell (MSC) exosomes as a novel therapeutic approach for the management of ATN. METHODS: A standardized process was employed to prepare 0.1 mL of exosomes, which were subsequently injected into bilateral regions of the patients' scalps at 0.5-1 cm intervals on a monthly basis. Each injection comprised a total volume of 5 mL, and all three patients underwent a minimum of four treatment sessions. The comparative efficacy of the treatment was evaluated using clinical photographs, dermatoscopy, and scanning electron microscopy (SEM) for all three patients post-intervention. RESULTS: The hair condition of the three patients demonstrated significant improvement, characterized by increased length and density, enhanced pigmentation with a reduced presence of dusty white dots, and the disappearance of dermoscopic black dots and broken hairs. SEM analysis revealed a remarkable recovery in the hair cuticle layers. At the 1-year follow-up, hair growth essentially remained normal. CONCLUSION: Exosomes derived from mesenchymal stem cells demonstrate efficacy in treating ATN, presenting a novel therapeutic approach for this condition.