Perioperative anxiety is associated with negative patient outcomes in Mohs micrographic surgery (MMS). Both pharmacologic and nonpharmacologic therapies have been used to alleviate perioperative anxiety in MMS.To systematically evaluate the efficacy of therapies aimed at reducing perioperative anxiety in MMS.Eligible articles were identified using PubMed MEDLINE, Cochrane Central Register of Controlled Trials, metaRegister of Controlled Trials, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform. All available studies investigating interventions to reduce perioperative anxiety during MMS were considered.Of the 183 abstracts identified and screened, 5 studies met inclusion criteria. Three studies reported a postintervention reduction in patient anxiety (midazolam, educational video, and personalized music). Two studies reporting on similar interventions did not find an effect.There is currently limited evidence to support either pharmacologic or nonpharmacologic therapy for alleviation of perioperative patient anxiety in MMS. Midazolam may provide patients a short-term benefit, though any estimate of the effect is very uncertain. Personalized music may be a promising nonpharmacologic intervention for future research.