This paper addresses the multi-floor process plant layout problem by developing four mixed integer linear programming (MILP) models. The problem involves decisions concerning the optimal spatial arrangement of process plant equipment and/or auxiliary units considering equipment connectivity, pumping and construction costs, and other factors. These considerations are extended to account for tall equipment items that span across floors and the availability of predefined production sections. The proposed models determine simultaneously the number of floors per section, floor areas per section, plot layout and site layout, and are applied to two case studies with up to 22 units and 6 production sections to demonstrate their applicability. (C) 2018 Published by Elsevier B.V. on behalf of Institution of Chemical Engineers.