TSP1 requires VWF to modulate arterial thrombus growth. The rate of thrombus growth in Tsp1^−/− mice was significantly decreased when compared with WT mice (*P < .05). Deficiency of VWF completely abrogated thrombus growth. The rate of thrombus growth was significantly decreased in Tsp1^-/-/Vwf^+/− compared with Tsp1^+/+/Vwf^+/− mice (P < .05), suggesting that ∼50% of VWF level in plasma is required for TSP1 to modulate later stages of thrombus growth. Of note Tsp1^−/−/Vwf^+/− mice exhibited markedly decreased rate of thrombus growth (^#P < .05 vs Tsp1^−/−). Data represent mean ± standard error of the mean. N = 10 to 13 mice/group. *P < .05 vs WT; ^#P < .05 vs Tsp1^−/−.