Tendon reconstruction surgery often requires healing of the tendon to bone. The development of a more rapid and strong interaction at the tendon to bone interface would be invaluable to patients having orthopaedic surgery. Therefore, our rationale was to modify sutures so that they would be anabolic for tendon to bone healing. It has been shown that silk stimulates bone formation in osteoblast cultures. In the current study, we tested the ability of silk and silk-RGD (arginine-glycine-aspartic acid) to stimulate human tenocyte adhesion, proliferation, and differentiation. A 1.3-fold increase in tenocyte adhesion was found on silk-RGD compared with tissue culture plastic. By 72 hours, proliferation had increased on all substrates but was particularly enhanced on silk-RGD compared with the control. At 6 weeks, Northern blot analysis of decorin and Type I collagen mRNA levels showed a 2-3-fold increase in message levels on silk-RGD and silk compared with tissue culture plastic. The data suggest cultured human tenocytes adhere, proliferate, and differentiate on silk and silk-RGD substrates. A suture material, such as silk, decorated with RGD, may have the potential to facilitate tendon-bone healing with widespread applications in tendon reconstruction surgery.