Continuous stirred tank reactors (CSTRs) can present operational problems as a result of complex open-loop behavior such as input and output multiplicities, parametric sensitivities, and nonlinear oscillations. It is sometimes appropriate to operate a chemical reactor at an unstable steady state. Traditionally, autotuning procedures for cascade-control strategies are applied using a sequential, one-loop-at-a-time method. Such a method, however, cannot be used on open-loop unstable systems because the secondary loop cannot stabilize the system when the primary loop is open. As a result, a new simultaneous autotuning procedure is proposed for the cascade controllers of open-loop unstable CSTR processes. This new approach can also be used for the autotuning of cascade-controlled open-loop stable systems, thereby covering a wide operation range for CSTR cascade-control systems.