This paper presents a systematic procedure that assists the designer of activated sludge plants to make critical decisions during the decision making process. By critical decisions we mean those (i) with a great influence on the overall design process and (ii) involving a set of options that satisfy the design objectives to a similar degree. Decision making for critical decisions is especially difficult when several design objectives (e.g., environmental, legal, economic, and technical) must be taken into account, i.e., when the evaluation of the most promising options is a multicriteria problem. The systematic procedure consists of three steps: (1) preliminary multiobjective optimization, where the most promising options (those located close to optimum conditions) are compared based on the results of dynamic simulation, (2) identification of the strong and weak points of each option by means of classification trees and the subsequent extraction of rules for each option, and (3) evaluation of the tradeoff between the improvement of the criteria identified as weak points of the option and the loss of the overall process performance through the integrated application of dynamic simulation and qualitative knowledge extracted during the design process. The capabilities of this new procedure are demonstrated with a case study where the (bio)reactor of an organic carbon and nitrogen removal plant is redesigned to achieve simultaneous organic carbon, nitrogen, and phosphorus removal. The results demonstrate how the new procedure supports the systematic analysis of critical decisions for activated sludge plant design.