In this paper, a single-iteration strategy is proposed for the design of a multi-loop PI controller to achieve the desired gain and phase margins for two-input and two-output (TITO) processes. To handle loop interactions, a TITO system is converted into two equivalent single loops with uncertainties drawn from interactions. The maximum uncertainty is estimated for the initial controller design in one loop and single-input and single-output (SISO) controller design is applied. This controller is substituted to other equivalent loop for design, and finally, the first loop controller is refined on knowledge of other loop controller. For SISO controller tuning, a new method is presented to determine the achievable gain and phase margins as well as the relevant controller parameters. Examples are given for illustration and comparison. (C) 2011 Elsevier Ltd. All rights reserved.