The medial sural artery perforator (MSAP) flap is a versatile fasciocutaneous flap, and yet is less commonly utilized than other free flaps in microvascular reconstructions of the head and neck. The aim is to conduct a high-quality Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) compliant systematic review comparing the use of the MSAP flap to other microvascular free flaps in the head and neck. Medline, EMBASE and Web of Science databases were searched to identify all original comparative studies comparing patients undergoing head and neck reconstruction with an MSAP flap to the radial forearm free flap (RFFF) or anterolateral thigh (ALT) flap from inception to February 2021. Outcome studied were the recipient-site and donor site morbidities as well as speech and swallow function. A total of 473 articles were identified from title and abstract review. Four studies met the inclusion criteria. Compared to the RFFF and the ALT flaps, the MSAP flap had more recipient-site complications (6.0% vs. 10.4%) but less donor-site complications (20.2% vs. 7.8%). The MSAP flap demonstrated better overall donor-site appearance and function than the RFFF and ALT flaps (P = 0.0006) but no statistical difference in speech and swallowing function following reconstruction (P = 0.28). Although higher quality studies reviewing the use of the MSAP flap to other free flaps are needed, the MSAP flap provides a viable and effective reconstructive option and should be strongly considered for reconstruction of head and neck defects.