The ability of vascular cells to withstand oxidative insults is critical to vascular health. It has emerged that NAD+-consuming enzymes such as sirtuins (SIRTs) and poly (ADP-ribose) polymerases (PARPs) are important regulators of cellular health. However, NAD+ content, which drives these reactions, can be compromised and strategies for overcoming this limitation in the vasculature do not exist. The purpose of this study was to determine if delivery of the natural precursor, nicotinamide riboside (NR), can control NAD+homeostasis in vascular cells to fuel resistance to oxidative stress. Using real-time PCR and Western blot analysis, we determined that human aortic endothelial cells (HAECs) and smooth muscle cells (SMCs) expressed nicotinamide riboside kinase 1, the enzyme required for NR to enter the cellular NAD salvage pathway. Next we established that subjecting HAECs to 0.25 mM H2O2 oxidative-stress insult led to an 87% drop in intracellular NAD+ levels by 30 mins, accompanied by a striking increase in nuclear PAR-chain accumulation. PARP inhibition (20 μM DPQ) abolished PAR-chain formation and revealed 5-fold higher NAD+ levels (p=0.0002), establishing PARP in NAD+ consumption in this model. To determine the protective potential of NR delivery, H2O2 exposed cells were pre-treated with 100 μM NR and tracked by time-lapse microscopy. This revealed 57% less cell-shrinkage (p<0.0001) and 60% less cell death (p=0.039) than vehicle control. An alkaline Comet Assay to evaluate DNA damage also revealed 56% lower tail moment at 3 hrs (p<0.0001), suggesting increased DNA repair efficiency. PARP inhibition mimicked NR’s beneficial effects on cell-shrinkage and viability but at the cost of DNA repair efficiency, demonstrated by 33% higher tail moment (p<0.0001). Interestingly, the beneficial effects of NR on cell survival and DNA repair were abrogated upon siRNA-mediated SIRT1 knock-down (KD). SIRT6 KD was similarly implicated in NR-mediated DNA repair. Furthermore NR delivery protected against oxidative-stress-induced senescence (58% less senescence-associated β-gal positive cells (p=0.007)) in a SIRT1 and SIRT6 dependant manner. NR delivery protects vascular cells from H2O2-induced cell death, cytoskeletal collapse and senescence and promotes DNA repair efficiency. This NAD+ fueling strategy may offer new opportunities for resisting oxidative-stress insults in the aging vasculature.