Background: New high-voltage power transmission lines will be introduced due to increasing demand for reliable and renewable energy supplies. Some residents associate non-specific health complaints with exposure to electromagnetic fields from nearby power lines. This study protocol describes the design and rationale of a prospective study investigating whether the introduction of a new power line triggers health responses in residents living nearby. Methods/Design. The study is designed as a quasi-experimental field study with two pretests during the construction of a new power line route, and two posttests after it has been put into operation. Key outcomes are self-reported non-specific somatic and cognitive health complaints, and attribution of these health complaints to a power line. The main determinant is proximity to the new power line route. One member of every household (n = 2379) residing in close proximity (0-500 meters) to the overhead parts of a new power line route in the Netherlands is invited to participate, as well as a sample of household members (n = 2382) residing farther away (500-2000 meters). Multilevel analysis will be employed to test whether an increase in key outcome measures is related to proximity to the line. Longitudinal structural equation models will be applied to test to what extent health responses are mediated by psychosocial health mechanisms and moderated by negative oriented personality traits. Discussion. This is the first study to investigate health responses to a new power line route in a prospective manner. The results will provide theoretical insight into psychosocial mechanisms operating during the introduction of an environmental health risk, and may offer suggestions to policymakers and other stakeholders for minimizing adverse health responses when introducing new high-voltage power lines. © 2014 Porsius et al.; licensee BioMed Central Ltd.