© 2017 Elsevier Inc. Objective Evaluate association between baseline quality of life (QOL) and changes in QOL measured by FACT-O TOI with progression-free disease (PFS) and overall survival (OS) in advanced epithelial ovarian cancer (EOC). Methods Patients enrolled in GOG-0218 with completed FACT-O TOI assessments at baseline and at least one follow-up assessment were eligible. Baseline FACT-O TOI scores were sorted by quartiles (Q1-4) and outcomes compared between Q1 and Q2-4 with log-rank statistic and multivariate Cox regression adjusting for age, stage, post-surgical residual disease size, and performance status (PS). Trends in FACT-O TOI scores from baseline to the latest follow-up assessment were evaluated for impact on intragroup (Q1 or Q2-4) outcome by log-rank analysis. Results Of 1152 eligible patients, 283 formed Q1 and 869 formed Q2-4. Mean baseline FACT-O TOI scores were 47.5 for Q1 vs. 74.7 for Q2-4 (P < 0.001). Q1 compared to Q2-4 had worse median OS (37.5 vs. 45.6 months, P = 0.001) and worse median PFS (12.5 vs. 13.1 months, P = 0.096). Q2-4 patients had decreased risks of disease progression (HR 0.974, 95% CI 0.953–0.995, P = 0.018), and death (HR 0.963, 95% CI 0.939–0.987, P = 0.003) for each five-point increase in baseline FACT-O TOI. Improving versus worsening trends in FACT-O TOI scores were associated with longer median PFS (Q1: 12.7 vs. 8.6 months, P = 0.001; Q2-4: 16.7 vs. 11.1 months, P < 0.001) and median OS (Q1: 40.8 vs. 16 months, P < 0.001; Q2-4: 54.4 vs. 33.6 months, P < 0.001). Conclusions Baseline FACT-O TOI scores were independently prognostic of PFS and OS while improving compared to worsening QOL was associated with significantly better PFS and OS in women with EOC.