45 patients scheduled for primary total knee arthroplasty (TKA) were randomized to one of three study groups to determine which of the three predetermined wound closure techniques was associated with the most robust incision perfusion rate immediately following surgery. The purpose of this study was to compare the running subcuticular technique, the vertical mattress technique, and the staple closure technique by evaluating baseline and peak perfusion rates via a laser-assisted indocyanine green angiography (LA-ICGA) immediately after designated wound closure. Results demonstrated that the running subcuticular technique correlated with the most robust perfusion rate (followed by vertical mattress closure and staple closure). Further trials are needed to investigate the clinical implications of this finding on wound healing.