This paper presents a heuristic approach based on the POPMUSIC framework for a large-scale Multi Depot Vehicle Routing Problem with Time Windows derived from real-world data. POPMUSIC is a very powerful tool for tackling large problem instances. A Memetic Algorithm is used as an optimizer in the POPMUSIC framework. It is shown that a population-based search combined with decomposition strategies is a very efficient and flexible tool to tackle real-world problems with regards to solution quality as well as runtime. Journal of the Operational Research Society ( 2009) 60, 934-943. doi:10.1057/palgrave.jors.2602633