Achieving universal access to safe drinking water is a global challenge, especially in rural areas of low-income countries. In Nepal, most rural households have access to a protected drinking water source. However, for 75% of the rural population, these sources are impacted by fecal and chemical contaminants. This chapter describes 4 years of applied research on drinking water quality in Mid-Western Nepal, in collaboration with Helvetas Swiss Intercooperation and the REACH: Improving Water Security for the Poor program. The aim of this project was to improve access to safe drinking water for rural households served by the Helvetas Water Resources Management Programme. The field activities were organized into three phases: a baseline characterization of microbial quality at water collection points and household water storage containers for 505 households; an investigation of households’ perceptions and practices regarding household water treatment; and controlled evaluation of a combined water safety intervention's impact on E. coli concentrations for five piped schemes. The interventions examined included solar-powered field laboratories, centralized data management, targeted infrastructure improvements, household filter promotion, a sanitation and hygiene behavior change campaign, and community-level orientation and training. By the end of the study period the share of taps and storage containers meeting the WHO guideline for microbial safety increased from 7% to 50% and from 17% to 53%, respectively. These findings indicate that a combination of tailored interventions can effectively reduce fecal contamination at the points of collection and consumption for piped supplies in remote rural communities.