We compare the most commonly used proteomic sample preparation strategies such as classical in solution digest protocols, SPEED, FASP, STrap, SP3, as well as the commercially available kits iST (PreOmics) and EasyPep (Thermo Scientific) in their efficacy to extract proteomes from HeLa cells. We find a remarkably good performance of the majority of the protocols with high reproducibility, little method dependencies and low levels of artifact formation. Despite these similarities we observe significant differences in the recovery of specific sets of proteins in a k-means cluster analysis.