Trauma or lesion resection often causes complex wounds with deep soft tissue defects in extremities. Simply covering with a skin flap will leave a deep dead space resulting in infection, non-healing wounds, and poor long-term outcomes. Thus, effectively reconstructing complex wounds with dead space leaves a clinical challenge. This manuscript presents our experience using chimeric medial sural artery perforator (cMSAP) flap, to reconstruct complex soft tissue defects of the extremities, thereby exploring broader analysis and indications for future reference. Between March 2016 and May 11, 2022, patients (8 males and 3 females) with a mean age of 41 years (range from 26 to 55 years) underwent reconstructive surgery with the cMSAP flap. The cMSAP flap consists of an MSAP skin paddle and a medial sural muscle paddle. The size of the MSAP skin paddle ranged between 9 × 5cm and 20 × 6cm, and the size of the medial sural muscle paddle ranged between 2 × 2cm and 14 × 4cm. Primary closure of the donor site was achieved in all cases. Of the 11 patients, the cMSAP flap survived in 10 cases. The vascular compromise occurred in one special case and was treated with surgical procedures. The mean follow-up duration was 16.5months (range of 5-25 months). Most patients present satisfactory cosmetic and functional results. The free cMSAP flap is a good option for reconstructing complex soft tissue defects with deep dead space in extremities. The skin flap can cover the skin defect, and the muscle flap can fill the dead space against infection. In addition, three types of cMSAP flaps can be used in a broader range of complex wounds. This procedure can achieve an individualised and three-dimensional reconstruction of the defects and minimise the donor site morbidities.