Poly(p-dioxanone) (PDO), a versatile poly(ester-ether), has been used for a variety of biomedical applications. Functional performance of this semicrystalline polymer heavily relies on its crystallinity and crystalline behavior. Upon extended exposure to heat above the glass transition temperature and below the melting temperature, PDO undergoes thermal annealing. Isothermal studies at elevated temperatures utilizing a differential scanning calorimeter were performed in order to determine the most appropriate conditions to anneal the polymer. Of the investigated mechanical properties, yield strength and elastic modulus were significantly improved with annealing. This improvement over nonannealed samples was also observed with samples subjected to phosphate-buffered saline (PBS) solution at 37 degrees C for 2 weeks. After 1 month continuous immersion in PBS solution, the PDO became brittle with deteriorated elongation at break but maintained yield strength and modulus. At 2 months, all specimens exhibited cracks on the surface and a complete loss of mechanical strength. The enhanced yield strength by thermal annealing creates more opportunities for PDO in medical device implants particularly in applications involving soft tissue repair and hemostasis. POLYM. ENG. SCI., 59:1701-1709 2019. (c) 2019 Society of Plastics Engineers