An experimental investigation on the effects of in vitro hydrolytic and enzymatic degradation on mechanical properties of polyglactin 910 monofilament sutures was performed by conducting nanoindentation studies using an atomic force microscope (AFM). For hydrolytic degradation, the sutures were incubated in phosphate buffered saline (PBS) solution at three different pH conditions, 5, 7.4, and 10. For enzymatic degradation, esterase was employed at pH condition of 7.4. The property of the sutures changed with time at different conditions were investigated by nanoindentation, tensile test experiments, image analysis using both of scanning electron microscopy (SEM) and AFM, and also Fourier transform infrared spectroscopy (FTIR). The effects of degradation on gradation of Young's modulus values across the cross section of the sutures were studied by doing progressive nanoindentation from center to surface. FTIR studies revealed the formation of new hydroxyl bonds due to both hydrolytic and enzymatic degradations. Nanoindentation results indicated that the degradation does not cause a gradient of Young's modulus of the polyglactin 910 monofilament sutures across the cross section from center to surface at different degradation times for both hydrolytic and enzymatic degradations. However, in general, the Young's modulus of all samples was decreased over 4 weeks of degradation. The microscopic evaluation of the samples also showed both qualitative changes in surface morphology and quantitative changes in surface roughness on the surface of degraded sutures. This study provided a deep understanding of the polyglactin sutures subjected to in vitro hydrolytic and enzymatic degradation, and also opened a new avenue to study the biomaterials at nano-scale.