The building sector contributes a large proportion of the world’s total final energy consumption. As aresult, considerable attention has been paid to energy efficiency in the building sector. At the current stage,building retrofitting is the most feasible and cost-effective method to improve building energy efficiency.This paper presents a multi-objective optimization model for life-cycle cost analysis and retrofitting plan-ning of buildings. A net present value (NPV) based economic analysis taking life-cycle cost into account isintroduced to formulate the objective functions. In addition, a combination of multiple alternative meas-ures for each retrofitting intervention is considered in determining the optimal solution. The presentedmodel aims at maximizing both energy savings and economic benefits during a selected time frame. Itallows decision makers to make best use of the available budget. A differential evolution (DE) algorithmis proposed to solve this optimization problem. The result of the case study illustrates the effectivenessof the multi-objective optimization model to support the planning of energy-efficient and cost-effectivebuilding retrofitting projects.