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This article examines the association between perceptions of neighborhood problems and health-related quality of life (HRQOL) in a sample of New Zealand residents (n = 692). A modified version of the Neighborhood Problems Scale (originally developed by Steptoe and Feldman, 2001) and the World Health Organization Quality of Life (WHOQOL-BREF) were used to assess perceptions of neighborhood problems and HRQOL, respectively. Multiple linear regression analyses were conducted to assess the association between perceptions of neighborhood problems and each of the WHOQOL-BREF domains: physical, psychological, social, and environmental HRQOL. Perceptions of neighborhood problems and gender interacted in the physical HRQOL regression; the negative association between perceived neighborhood problems and physical HRQOL was stronger for males compared with females. Neighborhood problems were also negatively predictive of psychological, social, and environmental HRQOL. Overall, our results suggest that the various aspects of well-being may be influenced by perceptions of neighborhood problems.