The physics reach of the LHC requires unprecedented luminosity and beam intensity in proton-proton collisions. The maximum intensity in the LHC is directly coupled to the maximum peak beam loss rate and the cleaning efficiency from the collimation system. A sophisticated LHC collimation system is implemented in two cleaning insertions and in the experimental areas. In a first phase 88 collimators are installed, being controlled by 344 stepping motors in total. The work of this PhD analyzes the achievable cleaning efficiency with realistic imperfections, defines the required collimator settings and establishes available tolerances for collimator setup and transient optics changes. An optimal setup strategy can optimize cleaning efficiency, ensure passive protection, maximize tolerances, minimize the required beam time for setup of the system and support the expected evolution in LHC beam intensity. Such an optimized strategy is described.