Background: The aim of this study was to develop a minimally invasive hydrogel system that can release strontium ions, an element that has been shown to increase osteoblast proliferation and prohibit bone resorption, in a controlled manner. Methods: SrCO3 was selected as the salt of choice due to potential acid neutralization reaction between SrCO3 and degradation by-products of methoxy(polyethylene glycol)-co-poly(lactic-co-glycolic acid) (mPEG-PLGA): namely, lactic acid and glycolic acid. SrCO3 was incorporated into mPEG-PLGA hydrogel, and the system was assessed for gelation properties, drug release and biocompatibility. Results: SrCO3 incorporation at hydrogel to SrCO3 ratios of 5:1, 3:1 and 1:1 (wt%) did not compromise the thermosensitivity of mPEG-PLGA hydrogels. Furthermore, incorporation of SrCO3 at 1:1 ratio prevented copolymer self-catalysis and decreased hydrogel weight loss from 85% to 61% in vitro after 30 days. During the 30-day time frame, zero-order strontium release was observed and was correlated to hydrogel degradation and acidity. The addition of SrCO3 also improved in vivo hydrogel biocompatibility, due to moderation of acidic microenvironment and amelioration of in flammatory response. Conclusions: These results showed that the described system is suitable for the extended release of strontium and exhibits potential for localized treatment for osteoporosis or as a bone void filler.