Silver nanoparticle (AgNP) based antibacterial surfaces were fabricated using plasma polymerization technology and their effects on differentiation of human bone-marrow derived mesenchymal stem cells (hMSCs) were investigated in this study. The results showed that AgNP coated surfaces do not affect the initial adhesion, spreading and proliferation of hMSCs. Furthermore, the silver coated surface promoted adipogenic differentiation of hMSCs as demonstrated by more accumulation of lipid droplets and upregulation of adipogenesis-related genes such as peroxisome proliferator activated receptor gamma (PPARγ), adipocyte determination and differentiation factor (ADD1) and CCAAT/enhancer binding protein alpha (C/EBPα). In addition, silver incorporation activated the expression of antioxidant enzymes as a consequence of the accumulation of intracellular reactive oxygen species (ROS) in adipogenic induced cells, which was correlated with the enhanced adipogenic capacity of hMSCs. ROS generation was enhanced due to silver ion release and consequently reduced osteogenesis at the early stage after 7 days of osteogenic induction as a result of reducing alkaline phosphatase (ALP) activity. However, the differentiation and mineralization capacity of osteoblasts were restored after 14 days of osteogenic induction, which indicated that adipogenesis favors intracellular ROS accumulation mediated by silver coatings compared to osteogenesis. None of the osteogenic related genes was affected by ROS mediated by AgNP dissolution. The findings in this work are instructive for the use of silver as an antibacterial agent in the areas of tissue engineering, stem cell therapies and implantable biomedical devices.