Enterolactone and enterodiol, mammalian lignans derived from dietary sources such as flaxseed, sesame seeds, kale, broccoli, and apricots, may impede tumor proliferation by inhibiting activation of nuclear factor kappa B ($NF{kappa}B$) and vascular endothelial growth factor (VEGF). We examined the associations between urinary enterolactone and enterodiol with prostatic tumor expression of $NF{kappa}B$, VEGF, and Ki67 among 147 patients with prostate cancer who participated in a presurgical trial of flaxseed supplementation (30 g/day) for ~30 days. Urinary enterolignans and tissue biomarkers were determined by high-performance liquid chromatography and immunohistochemistry, respectively. After supplementation, we observed significant correlations between intakes of plant lignan and urinary concentrations of total enterolignans (${ ho}$ = 0.677, P < .0001), enterolactone (${ ho}$ = 0.676, P < .0001), and enterodiol (${ ho}$ = 0.628, P < .0001). Importantly, we observed that total urinary enterolignans and enterolactone were significantly and inversely correlated with Ki67 in the tumor tissue (${ ho}$= -0.217, P = .011, and ${ ho}$= -0.230, P = .007, respectively), and a near-significant inverse association was observed for enterodiol (${ ho}$ = - 0.159, P = .064). An inverse association was observed between enterolactone and VEGF (${ ho}$= -0.143, P = .141), although this did not reach statistical significance. We did not observe an association between enterolignans and $NF{kappa}B$. In conclusion, flaxseed-derived enterolignans may hinder cancer cell proliferation via VEGF-associated pathways.