Controlled release silica sol-gels are room temperature processed, porous, resorbable, and biocompatible materials. Many molecules including drugs, proteins, and growth factors can be released from sol-gels, and the quantity and duration of the release can vary widely. Processing parameters render these release properties exquisitely versatile . The synthesis of controlled release sol-gels involves several steps: an acid-catalyzed hydrolysis to form a sol with the molecules included, followed by casting, aging, and drying. Additional steps such as grinding and sieving are required to produce sol-gel granules of a desirable size. In this study, we focus on the synthesis of controlled release sol-gel microspheres by using a novel process, which involves only two steps:sol formation followed by emulsification. Sol-gel microspheres containing either vancomycin (antibiotic) or bupivacaine (analgesic) were successfully synthesized via this synthesis route. Both drugs showed controlled, load-dependent and time-dependent release from the microspheres. The in vitro release properties of sol-gel microspheres were different from those of sol-gel granules produced by grinding and sieving. In comparison to a fast, short-term release from the granules, the release from the microspheres was slower and of longer duration. In addition, the degradation rate of microspheres was significantly slower than that of the granules. These data enable the use of sol-gel powders for controlled long-term release.