Background: Standard treatment for advanced ovarian cancer (aOC) includes primary cytoreductive surgery followed by chemotherapy (PDS > CTX). There is strong evidence that this strategy is accompanied by high risk for early failure in some patients (pts) but prospective multicenter data for this specific question are lacking. Methods: 64 AGO-sites prospectively registered pts with suspected aOC and collected following variables prior to start of therapy: age, Charlson Comorbidity Index (CCI), timed up and go test (TUG), ASA and ECOG performance score, weight, height, estimated ascites, albumin, creatinine, hemoglobin, leucocytes, platelets, CA125, patient reported outcome measures according to EORTC QLQ-C30 and OV28, hospital anxiety and depression score (HADS), physician-assessed suspected FIGO IV stage, abdominal pain requiring treatment, abdominal bloating, dyspnea and required palliative paracentesis (ascites, pleural effusions). Treatment followed according to investigator’s decision. Primary objective was to predict the unfavorable event of death or progression within 10 months after primary diagnosis. We applied univariate and multiple logistic regression with stepwise variable selection after multiple imputation of missing data in order to identify relevant predictors. Results: 223 pts with aOC FIGO IIIB to IVB and PDS were analyzed. Median age was 63 years (range 31-86). 52 (23.3%) pts experienced progression or death within 10 months from time of enrolment. In univariate regression, age (odds ratio (OR) 1.612 per 10 years), ASA (III vs I/II: OR 3.217), TUG (OR 1.087), body height (OR 0.541 per 10cm), ECOG (1 vs 0 OR 2.326, 2-3 vs 0 OR 4.102), estimated ascites ( > 500cc vs. none OR 2.811), paracentesis (OR 1.991), platelets (upper limit of normal (ULN) vs norm or < lower limit of normal (LLN) OR 1.998), albumin ( < LLN vs norm or > ULN OR 2.053), creatinine ( > ULN vs norm OR 3.969) and baseline QoL single-item subscales appetite loss (“very much” vs “not at all” OR 2.611), constipation (“quite a bit” vs “not at all” OR 4.903), and multi-item subscales global health status (OR 0.982 per 1 point) and nausea/vomiting (OR 1.013 per 1 point) were significant (p < 0.05). Multiple logistic regression identified age (OR 1.459 per 10 years), ASA (III vs I/II: OR 2.427), constipation (“quite a bit” vs “not at all” OR 3.786) and global health (OR: 0.985 per 1 point) as independent predictors of progression or death within 10 months after primary diagnosis (p < 0.05). Conclusions: A significant proportion of aOC pts undergoing PDS > CTX are at high-risk for early failure. The finding of independent risk factors including self-ratings of QoL at time of diagnosis should be confirmed and tested against other models to facilitate a more tailored treatment of high-risk pts and design of future trials in aOC. Clinical trial information: NCT02828618.