Climate change is expected to increase precipitation extremes, threatening water quality. In low resource settings, it is unclear which water sources are most vulnerable to contamination following rainfall events. We evaluated the relationship between rainfall and drinking water quality in southwest Guatemala where heavy rainfall is frequent and access to safe water is limited. We surveyed 59 shallow household wells, measured precipitation, and calculated simple hydrological variables. We compared Escherichia coli concentration at wells where recent rainfall had occurred versus had not occurred, and evaluated variability in the association between rainfall and E. coli concentration under different conditions using interaction models. Rainfall in the past 24 hours was associated with greater E. coli concentrations, with the strongest association between rainfall and fecal contamination at wells where pigs were nearby. Because of the small sample size, these findings should be considered preliminary, but provide a model to evaluate vulnerability to climate change.