We examine the spin-dependence of b-quark production at large transverse momentum in polarized proton-proton collisions. The leading-order (LO) 2 -> 2 subprocesses, g + g -> Q + Q-bar and q+ q-bar -> Q + Q-bar have a large `analyzing power', as measured by the average spin-spin asymmetry <a-hat_{LL}>, at large p_T, approaching -100%. The contributions from next-to-leading order (NLO) 2 -> 3 processes are also discussed and found to be dominated at large transverse momentum by subprocesses with a large and positive partonic level spin asymmetry leading to strong cancellations with the LO predictions. The results suggest that b-quark production might constitute an interesting test of the spin-dependence of NLO QCD but they also point up the importance of a full calculation of the complete O(\alpha_S^3) spin-dependent corrections for a successful extraction of the polarized gluon distribution. Similarities to gluino pair production are also briefly discussed.