To date there are no approved antiviral drugs for the treatment of Ebola virus disease (EVD). Based on our in vitro evidence of antiviral activity of interferon (IFN)-ß activity against Ebola virus, we conducted a single arm clinical study in Guinea to evaluate the safety and therapeutic efficacy of IFN β-1a treatment for EVD. Nine individuals infected with Ebola virus were treated with IFN β-1a and compared retrospectively with a matched cohort of 21 infected patients receiving standardized supportive care only during the same time period at the same treatment unit. Cognizant of the limitations of having treated only 9 individuals with EVD, the data collected are cautiously considered. When compared to supportive care only, IFN β-1a treatment seemed to facilitate viral clearance from the blood and appeared associated with earlier resolution of disease symptoms. Survival, calculated from the date of consent for those in the trial and date of admission from those in the control cohort, to the date of death, was 19% for those receiving supportive care only, compared to 67% for those receiving supportive care plus IFN β-1a. Given the differences in baseline blood viremia between the control cohort and the IFN-treated cohort, an additional 17 controls were included for a subset analysis, from other treatment units in Guinea, matched with the IFN-treated patients based on age and baseline blood viremia. Subset analyses using this expanded control cohort suggests that patients without IFN β-1a treatment were ~ 1.5–1.9 fold more likely to die than those treated. Viewed altogether the results suggest a rationale for further clinical evaluation of IFN β-1a.