This research was conducted in eight rivers and eight wells in the province of Los Santos, an agricultural region, with a high consumption of pesticides. In the research, it is proposed to determine the influence of hardness of water in rivers and wells, used as a medium, for pesticide applications, and study its effect on the efficacy of pesticides. The sampling was carried out considering the dry and rainy season in the period between February 2016 and February 2017. The water samples were collected in the Taguada, Bajo Güera, Faldar, Estibaná, Tebario and Río Gato rivers, district of Macaracas; in the Tonosí River and the La Bonita stream and a well located in Tonosí Centro, Tonosí district; a well located in Tablas Abajo district of Las Tablas; wells in Llano Abajo, La Pacera and Ciénega Larga in Guararé and two wells, one Sabana Grande and in Tres Quebradas district of Los Santos. The samples were analyzed in the laboratories of Quality Control of Pesticides and Analysis of Residues of Pesticides in Plants and Vegetable Products of the National Direction of Plant Health. Therefore, the average hardness in wells resulted in hard water and rivers medium hard, according to the scale established by the EPA. There was more active ingredient reduction from dimethoate solutions of well water than deionized water. Equally occurred with river water and well water in solutions with glyphosate.