Abstract: A non-stationary climate imposes considerable challenges regarding potential public health concerns. The El Niño Southern Oscillation (ENSO) cycle, which occurs every 2 to 7 years, correlates positively with occurrences of the waterborne disease cholera. The warm sea surface temperatures and extreme weather associated with ENSO create optimal conditions for breeding the Vibrio cholerae pathogen and for human exposure to the pathogenic waters. This work explored the impacts of ENSO on cholera occurrence rates over the past 50 years by examining annual rates of suspected cholera cases per country in relation to ENSO Index values. This study provides a relationship indicating when hydrologic conditions are optimal for cholera growth, and presents a statistical approach to answer three questions: Are cholera outbreaks more likely to occur in an El Niño year? What other factors impact cholera outbreaks? How will the future climate impact cholera incidence rates as it relates to conditions found in ENSO? Cholera outbreaks from the 1960s to the present are examined focusing on regions of Central and South America, and southern Asia. By examining the predictive relationship between climate variability and cholera, we can draw conclusions about future vulnerability to cholera and other waterborne pathogenic diseases.