XENON100 is a two-phase time projection chamber with a 62 kg liquid xenon target to search for Dark Matter interactions. Both scintillation and ionization signals are recorded to allow interaction vertex reconstruction in three dimensions. Fiducialization of the target volume results in the lowest background level of any running Dark Matter search experiment. In a 48 kg fiducial target and 100.9 days of live time, no evidence for Dark Matter is found. This leads to the strongest limit on elastic spin-independent WIMP-nucleon interactions for WIMP masses above ∼ 10 GeV/c2. Also, this data excludes inelastic Dark Matter scattering off sodium or iodine as an explanation of the DAMA modulation.