Background The medial sural artery perforator flap is a versatile option in reconstructive microsurgery. However, most reports of this flap have been limited by sample size. This study reviews the experience of a single large-volume center using the medial sural artery perforator flap and its variants for a variety of reconstructive purposes. Methods A retrospective review of all patients who received the medial sural artery perforator flap reconstruction between March of 2006 and July of 2014 was performed. Results Two-hundred medial sural artery perforator flaps were used at three anatomical regions: head and neck (n = 129), upper extremity (n = 47), and lower extremity (n = 24). Flaps were transferred as free (n = 189) and pedicled (n = 11). Overall flap survival was 96 percent. Flap variants used included chimeric flap (n = 11) and dual skin paddle (n = 2). Plantaris tendon and saphenous/sural nerve graft were harvested in conjunction in 20 and seven patients, respectively. In 5 percent of the cases harvested in the conventional manner, a reliable perforator could not be found. Conclusions The medial sural artery perforator flap is a reliable, alternative workhorse flap for nearly any small- to medium-size defect. It can be harvested as free or pedicled and the option to include multiple tissue components further expands its versatility. Clinical question/level of evidence Therapeutic, IV.