The application of groundwater vulnerability methods has great importance for the sanitary protection zones delineation of karstic sources. Source vulnerability assessment of karst groundwater has mainly relied on the European approach (European Cooperation in Science and Technology—COST action 620), which includes analysis of the K factor, which refers to water flow through the saturated zone of the karst system. In the paper, two approaches to groundwater vulnerability assessment have been applied, COP + K and TDM (Time-Dependent Model) methods, to produce the most suitable source vulnerability map that can be transformed into sanitary protection zones maps. Both methods were tested on the case example of Blederija karst spring in Eastern Serbia. This spring represents a classical karst spring with allogenic and autogenic recharge. Dual aquifer recharge points out the necessity for the inclusion of the vulnerability assessment method created especially for the assessment of karst groundwater. Obtained vulnerability maps show similar results, particularly in the spring and the ponor areas, and these zones are most important for future protection. The COP + K method brings out three vulnerability classes that can be directly transformed into three sanitary protection zones. Contrary to the previous one, the TDM method uses water travel time as a vulnerability degree. The results show that the final map can be easily used to define sanitary zones considering different national legislation.