The development of minimally invasive therapeutics for orthopedic clinical conditions has substantial benefits, especially for osteoporotic fragility fractures and vertebral compression fractures. Poly(ester urethane)urea (PEUUR) foams are potentially useful for addressing these conditions because they cure in situ upon injection to form porous scaffolds. In this study, the effects of water concentration and polyester triol composition on the physicochemical, mechanical, and biological properties of PEUUR foams were investigated. A liquid resin (lysine diisocyanate) and hardener (poly(epsilon-caprolactone-co-glycolide-co-DL-lactide) triol, tertiary amine catalyst, anionic stabilizer, and fatty acid-derived pore opener) were mixed, and the resulting reactive liquid mixture was injected into a mold to harden. By varying the water content over the range of 0.5 to 2.75 parts per hundred parts polyol, materials with porosities ranging from 89.1 to 95.8 vol-% were prepared. Cells permeated the PEUUR foams after 21 days post-seeding, implying that the pores are open and interconnected. In vitro, the materials yielded non-cytotoxic decomposition products, and differences in the half-life of the polyester triol component translated to differences in the PEUUR foam degradation rates. We anticipate that PEUUR foams will present compelling opportunities for the design of new tissue-engineered scaffolds and delivery systems because of their favorable biological and physical properties.