Background: In 2010, a randomized trial demonstrated no difference in survival in advanced ovarian cancer patients treated with neoadjuvant chemotherapy (NAC) or primary debulking surgery (PDS). We examined the use and effectiveness of NAC in clinical practice over time. Methods: Prospective cohort study of women with stage IIIC/IV ovarian cancer treated at National Comprehensive Cancer Network (NCCN) institutions between 2003-2012. We examined the use (N = 961) and outcomes (N = 414) of NAC + interval debulking (IDS) +/- adjuvant chemotherapy versus PDS +/- adjuvant chemotherapy. Propensity score matching was used to balance observed confounders between groups in the outcomes analyses and trial participants excluded. Cox regression, logistic regression, and Fisher’s exact test were used to examine overall survival, residual disease, and perioperative morbidity in the matched sample. Results: Use of NAC+IDS increased from 0-39% between 2003-2010, and rose to 53% (stage IIIC) and 58% (stage IV) in 2011-2012. Adoption of NAC+IDS varied by institution from 0%-29% (stage IIIC, P < 0.001) and 13%-48% (stage IV, P = 0.04). After propensity-score adjustment, NAC+IDS was associated with lower survival in stage IIIC disease, compared with PDS (median 31 vs. 50 months, hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.05-2.24), and comparable survival in stage IV disease (median 43 vs. 32 months, HR 0.78, 95% CI 0.50-1.22). NAC+IDS was associated with higher odds of an R0 resection [odds ratio (OR): 2.26, 95% CI 1.28-3.98, stage IIIC; OR 4.03, 95% CI 1.73-9.38, Stage IV), and fewer ostomies (adjusted rates: 3% vs. 9%, P = 0.11, stage IIIC and 3% vs. 11%, P = 0.06, stage IV). Readmission rates were lower in NAC+IDS, compared with PDS (adjusted rates: 2% vs. 16% for stage IIIC and 2% vs 15% for stage IV, both P < 0.001). Conclusions: NAC+IDS use increased significantly at NCCN centers between 2003-2012. In this observational study, overall survival was comparable in patients with stage IV disease, and NAC+IDS was associated with lower ostomy rates and perioperative morbidity in stage IIIC and IV disease. NAC+IDS was associated with decreased survival in patients with stage IIIC disease, however additional selection bias may remain after propensity-score matching.