OBJECTIVE: To assess if the angiogenic factors vascular endothelial growth factor (VEGF) and D-dimer are predictive of persistent disease, early relapse, and survival in patients with ovarian cancer who achieve a complete clinical remission after first-line chemotherapy. METHODS: Serum levels of VEGF and D-dimer were assessed by ELISA in 62 patients who completed first-line chemotherapy and underwent second-look laparotomy at Duke University Medical Center. Cox Proportional Hazards Modeling was utilized to determine if VEGF and/or D-dimer levels could predict disease-free and overall survival. The Kaplan-Meier method was used to estimate median survival. The Wilcoxon test was used to determine if a significant difference existed in median VEGF and D-dimer levels between patients with positive and negative second-look operations. RESULTS: Forty (65%) of the 62 women who underwent second-look laparotomy had persistent disease. The median VEGF levels were 264 pg/ml (range 109-896 pg/ml) in the group with negative second looks compared to 390 pg/ml (range 99-1011 pg/ml) in those with positive second-looks (P = 0.1). High levels of VEGF were marginally associated with the presence of persistent (P = 0.10) and gross (P = 0.07) disease at the time of second look laparotomy. After adjusting for CA125, women with high VEGF serum levels had a worse overall survival (P = 0.004). CONCLUSIONS: This study suggests that serum VEGF may be a clinically important marker for persistent disease and is predictive of survival in ovarian cancer patients after first-line chemotherapy.