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Background: Few prospective studies have compared poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors to chemotherapy for the treatment of BRCA1-mutated or BRCA2-mutated ovarian carcinoma. We aimed to assess rucaparib versus platinum-based and non-platinum-based chemotherapy in this setting. Methods: In this open-label, randomised, controlled, phase 3 study (ARIEL4), conducted in 64 hospitals and cancer centres across 12 countries (Brazil, Canada, Czech Republic, Hungary, Israel, Italy, Poland, Russia, Spain, Ukraine, the UK, and the USA), we recruited patients aged 18 years and older with BRCA1-mutated or BRCA2-mutated ovarian carcinoma, with an Eastern Cooperative Oncology Group performance status of 0 or 1, and who had received two or more previous chemotherapy regimens. Eligible patients were randomly assigned (2:1), using an interactive response technology and block randomisation (block size of six) and stratified by progression-free interval after the most recent platinum-containing therapy, to oral rucaparib (600 mg twice daily) or chemotherapy (administered per institutional guidelines). Patients assigned to the chemotherapy group with platinum-resistant or partially platinum-sensitive disease were given paclitaxel (starting dose 60–80 mg/m2 on days 1, 8, and 15); those with fully platinum-sensitive disease received platinum-based chemotherapy (single-agent cisplatin or carboplatin, or platinum-doublet chemotherapy). Patients were treated in 21-day or 28-day cycles. The primary endpoint was investigator-assessed progression-free survival, assessed in the efficacy population (all randomly assigned patients with deleterious BRCA1 or BRCA2 mutations without reversion mutations), and then in the intention-to-treat population (all randomly assigned patients). Safety was assessed in all patients who received at least one dose of assigned study treatment. This study is registered with ClinicalTrials.gov, NCT02855944; enrolment is complete, and the study