Objective To evaluate the efficacy of in situ regenerative therapy in refractory orthopedic wounds in children.Methods Sixty children with refractory wounds admitted to our department from January 2020 to July 2021 were recruited and randomly assigned to receive in situ regenerative therapy (observation group) and vacuum sealing drainage (VSD) (control group). Outcome measures included postoperative recovery, cytokine levels, visual analogue scale (VAS), and complications.Results In situ regenerative therapy achieved significantly faster growth of fibrous connective tissue, shortened time of wound healing, as well as a higher rate of flap formation as compared with VSD (P < 0.05). The levels of IL-6/8 in wound tissues treated by in situ regenerative therapy were lower than those by VSD (P < 0.05). 83.3% of refractory wounds were treated efficiently by in situ regenerative therapy as compared with VSD(66.7%). Lower pain scores and secretion scores achieved by in situ regenerative therapy(P < 0.05).Conclusion In situ regenerative therapy is an effective technology for treating pediatric refractory orthopedic wounds, which promotes the growth of fibrous connective tissue, shortens the healing time, as well as reduces the inflammatory response of local tissues.