Background: Millions of people are bitten by venomous snakes annually, causing high mortality and disability, but the true burden of this neglected health issue remains unknown. Since 2015, Médecins Sans Frontières has been treating snakebite patients in a field hospital in north-west Ethiopia. Due to the poor market situation for effective and safe antivenoms for Sub-Saharan Africa, preferred antivenom was not always available, forcing changes in choice of antivenom used. This study describes treatment outcomes and the effectiveness and safety of different antivenoms used. Methodology / Principal findings: This retrospective observational study included 781 snakebite patients presenting at the field hospital between 2015 and 2019. Adjusted odds ratios, 95%-CI and p-values were used to compare the treatment outcome of patients treated with Fav-Afrique (n = 149), VacSera (n = 164), and EchiTAb-PLUS-ICP (n = 156) antivenom, and to identify the risk of adverse reactions for each antivenom. Whereas only incidental snakebite cases presented before 2015, after treatment was made available, cases rapidly increased to 1,431 in 2019. Envenomation was mainly attributed to North East African saw-scaled viper (Echis pyramidum) and puff adder (Bitis arietans). Patients treated with VacSera antivenom showed lower chance of uncomplicated treatment outcome (74.4%) compared to Fav-Afrique (93.2%) and EchiTAb-PLUS-ICP (90.4%). VacSera and EchiTAb-PLUS-ICP were associated with 16- and 6-fold adjusted odds of treatment reaction compared to Fav-Afrique, respectively, and VacSera was weakly associated with higher odds of death. Conclusions / Significance: Snakebite frequency is grossly underreported unless treatment options are available. Although EchiTAb-PLUS-ICP showed favorable outcomes in this retrospective analysis, prospective randomized trials are needed to evaluate the effectiveness and safety of the most promising antivenoms for Sub-Saharan Africa. Structural investment in sustained production and supply of antivenom is urgently needed. Author summary: Snakebite is an important but highly neglected medical problem, causing high morbidity and mortality in low-and-middle income countries all over the world, including Ethiopia. When bitten by a venomous snake, appropriate treatment with the correct antivenom is crucial. However, in Ethiopia the correct antivenom is not always available due to low access to health facilities in rural areas. Even if antivenom is available, patients can often not afford it due to the high costs of clinical effective antivenoms. This study explores the effectiveness of three different antivenoms, Fav-Afrique, VacSera and EchiTAb-PLUS-ICP, and provides insights in factors that might influence the outcome of the snakebite treatment. This study shows that patients treated with VacSera antivenom have a higher chance of an adverse outcome of the treatment. Much more research on snakebite epidemiology and the effectiveness of antivenoms should be conducted, aiming to alert governments and antivenom manufacturers that this is a serious problem which cannot be ignored any longer. [ABSTRACT FROM AUTHOR]