This randomized, controlled trial evaluated four experimental therapeutics for Ebola virus disease (EVD) in the Democratic Republic of Congo during an outbreak that began in August 2018. Patients were randomly assigned to receive either ZMapp, remdesivir, MAb114, or REGN-EB3. The primary endpoint was death at 28 days. The trial enrolled 681 patients from November 20, 2018, to August 9, 2019. The data and safety monitoring board recommended terminating random assignment to ZMapp and remdesivir after an interim analysis showed superior efficacy of MAb114 and REGN-EB3 compared to ZMapp. At 28 days, death occurred in 35.1% of patients in the MAb114 group, 49.7% in the ZMapp group, and 33.5% in the REGN-EB3 group. Patients with shorter symptom duration, lower viral load, and better renal function had improved survival. Four serious adverse events were potentially related to the trial drugs. The study demonstrated that MAb114 and REGN-EB3 were superior to ZMapp in reducing mortality from EVD, highlighting the importance of early diagnosis and treatment.This randomized, controlled trial evaluated four experimental therapeutics for Ebola virus disease (EVD) in the Democratic Republic of Congo during an outbreak that began in August 2018. Patients were randomly assigned to receive either ZMapp, remdesivir, MAb114, or REGN-EB3. The primary endpoint was death at 28 days. The trial enrolled 681 patients from November 20, 2018, to August 9, 2019. The data and safety monitoring board recommended terminating random assignment to ZMapp and remdesivir after an interim analysis showed superior efficacy of MAb114 and REGN-EB3 compared to ZMapp. At 28 days, death occurred in 35.1% of patients in the MAb114 group, 49.7% in the ZMapp group, and 33.5% in the REGN-EB3 group. Patients with shorter symptom duration, lower viral load, and better renal function had improved survival. Four serious adverse events were potentially related to the trial drugs. The study demonstrated that MAb114 and REGN-EB3 were superior to ZMapp in reducing mortality from EVD, highlighting the importance of early diagnosis and treatment.