The purpose of this study was to examine the association between exposure to high traffic noise levels in housing and the proportion of high annoyance and self-perceived health problems, through a survey applied to comparable groups of individuals with and without exposure, selected in residential buildings from urban Santiago, Chile. It was an observational, cross-sectional study. Buildings with sides exposed and unexposed to high traffic noise levels were considered. In each building, independent samples of dwellings from each side were selected. A questionnaire consisting of three parts was applied: socio-demographic and related characteristics, self-perceived health state, and annoyance caused by different sources including traffic noise. To assess association between exposure to traffic noise and each self-perceived health response (including high annoyance), multiple logistic and log-binomial regression analyses were applied, adjusting by sociodemographic and related variables. Four residential buildings were included, achieving a total of 425 respondents, 200 living in exposed dwellings and 225 living in unexposed dwellings. Adjusted significant association was found between exposure and high annoyance, high degree of problems with concentration, sleeping and feeling rested, presence of head or neck ache, and feelings of depression, anguish or neurosis.