Complications such as joint infection or delayed wound healing can lead to morbidity and elevated health care costs after total joint arthroplasty. The purpose of this study was to compare the quality of running knotless barbed suture vs standard monofilament suture wound closure with respect to wound drainage and healing complications after total joint arthroplasty. For this study, 1000 joint arthroplasty patients were prospectively randomized to have fascial, soft tissue, and skin closure with knotless barbed suture vs standard suture during the period 2016 to 2018. An absorptive dressing was used for 1 week postoperatively. Each dressing was weighed and the saturated surface area of the dressing measured. A total of 939 dressings were available for evaluation. Incisions were evaluated for wound healing at each postoperative visit. Of the 1000 joint arthroplasties performed, suture breakage or needle disengagement occurred similarly with the standard monofilament suture and the running barbed suture (13 times vs 6 times; P=.17). Dressings were weighed, and when standard monofilament sutures were used, an average of 1.2 g more postoperative bandage weight was recorded (P<.002). Postoperative wound complications including stitch abscess or wound irritation occurred more often with standard monofilament sutures than with running barbed sutures (16 times vs 5 times; P<.025). Optimal wound closure after joint replacement is critical to enhance soft tissue healing and minimize infection risk, which can be caused by excessive wound drainage. The positive results shown for the running barbed suture of this prospective study indicate the difference in quality of closure between the standard monofilament suture and the running barbed suture in hip and knee arthroplasty surgical sites. [Orthopedics. 2021;44(4):216-222.].