Multicasting K independent messages via multiple-input multiple-output channels to multiple users where each user already has a subset of messages as side information is studied. A general framework of constructing layered space-time index coding (LSTIC) from a large class of space-time block codes (STBC), including perfect STBC, is proposed. We analyze the proposed LSTIC and show that it provides minimum determinant gains that are exponential with the amount of information contained in the side information for any possible side information. When constructed over a perfect STBC, the proposed LSTIC is itself a perfect STBC and hence many desired properties are preserved. To illustrate, we construct LSTIC over the following well-known STBCs: Golden code; 3 × 3, 4 × 4, and 6 × 6 perfect STBCs; and Alamouti code. Simulation results show that the obtained side information gain can be well predicted by our analysis. © 1963-2012 IEEE.