BACKGROUND First metatarsophalangeal joint arthritis (FMTPA), also known as hallux rigidus, is the most frequent degenerative disease of the foot. Diagnosis is made through both clinical and radiological evaluation. Regenerative medicine showed promising results in the treatment of early osteoarthritis. The aim of the present study was to report the results of a case of FMTPA treated with the injection of autologous adipose-derived mesenchymal stem cells. CASE SUMMARY A gentleman of 50 years of age presented with a painful hallux rigidus grade 2 resistant to any previous conservative treatment (including nonsteroidal anti-inflammatory drugs and hyaluronic acid injections). An injection of autologous adipose-derived mesenchymal stem cells into the first metatarsophalangeal joint was performed. No adverse events were reported, and both function and pain scales improved after 9 mo of follow-up. CONCLUSION The FMTP joint injection of mesenchymal stem cells improved symptoms and function in our patient with FMTPA at 9 mo of follow-up.