The performance of electrocatalysts in fuel cells is not only determined by their efficiency under reaction conditions but also by their stability and potential degradation processes. To investigate these factors, molecular dynamics simulation are performed in order to study the adsorption and detachment behavior of 2-3 nm-sized Pt nanoparticles (NPs) on defective graphite supports with up to 13-atom large vacancies. Larger NPs show stronger adsorption with increasing vacancy size, particularly for surface-oxidized NPs (Pt/O ratio 1:1), due to additional van der Waals interactions alongside covalent Pt-C bonds at defect sites. Detachment simulations reveal that larger vacancy defects significantly increase the energy barrier for detachment, especially for non-oxidized 2 nm NPs, as more Pt atoms remain at the defect after detachment. Surface oxidation reduces detachment barriers by over 50%, while larger NPs generally show lower barriers. In aqueous environments, detachment barriers for non-oxidized NPs decrease, particularly with larger defects. These findings highlight the critical role of defect size and NP surface oxidation in stabilizing Pt-NPs on carbon supports, reducing material loss and preserving catalytically active material. Non-oxidized 2 nm NPs on large defects emerge as promising candidates for stable catalytic applications in both vacuum and aqueous environments, making defect and/or vacancy engineering a promising approach.