13 randomized controlled trials (n = 859 TKAs) were included in this meta-analysis to examine the safety and efficacy of using a pneumatic tourniquet in primary unilateral total knee arthroplasty and to determine the most appropriate protocol. TKA with tourniquet was associated with lower intraoperative blood loss and an approximate 5 minute reduction in operative time; however, analyses evaluating postoperative blood loss, total blood loss, and transfusion requirements demonstrated no significant difference between TKA with and without a tourniquet. A higher rate of surgical site infection was associated with tourniquet use.