Assessment of groundwater vulnerability to pollution is an effective tool for the delineation of groundwater protection zones. DRASTIC approach was used to determine vulnerability zones in Dire Dawa groundwater basin, a semiarid region of Ethiopia. Maps of the seven DRASTIC parameters were prepared. GIS-Arc-View was used for mapping and performing weighted-overlay analysis. The result of the analysis indicated that eastern part of the study area, in which Dire Dawa town is located, is highly vulnerable. A low aquifer vulnerability class was determined for the western portion of the study area as a result of greater groundwater depths, higher relative soil clay content, and relatively low recharge rates for this area. The area between the two zones is of medium vulnerability. Observed nitrate concentrations in boreholes are in accordance with the vulnerability map. Some of the boreholes in the Sabian well field (Dire Dawa area) already deliver groundwater with nitrate levels significantly exceeding health standards set by the World Health Organization, while boreholes in the western part (low vulnerability zone) contain almost no nitrate. The result of this study is useful for risk assessments and for the development of effective groundwater management strategies for this region and others like it.