Alpha-tocopherol (AT) was encapsulated with native (NIn), acetylated (AIn) or cross-linked (CIn) inulin (two degrees each) by spray-drying. A face central composite experimental design for each system (AT–NIn, AT–AIn1, AT–AIn2, AT–CIn1, and AT–CIn2) was evaluated to determine the influence of inlet air temperature and AT/coating material ratio on the AT encapsulation percentage (EP). The AT microspheres obtained under optimal conditions were characterized determining the AT EP, morphology and their release profile in a hydrophilic system. The AT encapsulating percentage reached values above 86% in all the systems studied. The acetylation and cross-linking of inulin improved slight but significantly the AT encapsulating percentage respect to native inulin. The release profiles showed biphasic behavior, being the first and second zone attributed to uncovered and encapsulated AT, respectively. The AT release was <15% (0–540 min) from all AT-inulin microparticles, corresponding mainly to superficial AT release, following Higuchi model consistent with a diffusional mechanism. AT release rate constant from AT–NIn microspheres was significantly lower than those of AT–AIn and AT–CIn. The AT release pattern suggest that the microparticles could be applied in the design of functional foods, preserving the nutritional role of AT.