Purpose To determine if impregnating a suture with a cross-linking agent, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC), improved suture pull-out strength and cell viability. Methods Canine flexor digitorum profundus tendons were cut in canine zone D, and a single suture loop was placed in each end, with sutures soaked in either saline or an EDC solution with a concentration of 1%, 10%, or 50%. Suture pull-out strength, stiffness, and elongation to failure was determined by pulling the loop until failure. Cytotoxicity of the EDC treatment was evaluated by suspending treated sutures over cultured tenocytes. Results Mechanical properties for the EDC-treated side were improved over controls when treated with the 10% and 50% EDC solutions. The ratio of dead to live cells was significantly increased at all distances from the suture for the 50% EDC-treated group. Conclusions Suture treated with a 10% EDC solution provided the best combination of mechanical reinforcement and limited toxicity. Clinical relevance Sutures so treated may improve the ability of a tendon repair to sustain early mobilization. (J Hand Surg Am. 2015;40(10):1986-1991. Copyright (C) 2015 by the American Society for Surgery of the Hand. All rights reserved.)