This paper proposes an extension of CRONE control and design for unstable, multiple time-delay multivariable plants with right half-plane (RHP) zeros. The CRONE control approach developed for multivariable square plants is based on third generation scalar CRONE methodology. The aim is to find a decoupling and stabilizing controller for the open-loop transfer matrix. Fractional order transfer functions are used to define all the components of the diagonal open-loop transfer matrix, beta(0i). Optimization gives the best fractional open-loop transfer matrix, beta. Finally, frequency-domain system identification is used to find a robust controller K=G(-1)beta. When the plant is inversed, time-delays and RHP poles or zeros can appear on the denominator of the transfer matrix. G(-1). To achieve a stable controller some time-delays, RHP zeros and unstable poles must be included within the diagonal transfer function of the open-loop transfer To assess the proposed design, the CRONE control approach is applied to a distillation example. matrix. (C) 2008 Elsevier B.V. All rights reserved.