With this research I tested the hypothesis that individual preferences for specific ecosystem components and restorative environments are significantly associated with quality of life (QOL). A total of 379 human subjects responded to a structured 18-item questionnaire on topophilia and to the 26-item World Health Organization's Quality of Life (WHOQOL-Bref) instrument. Confirmatory factor analyses revealed four domains of topophilia (ecodiversity, synesthetic tendency, cognitive challenge, and familiarity) and four domains of QOL (physical, psychological, social, and environmental). Synesthetic tendency was the strongest domain of topophilia, whereas the psychological aspect of QOL was the strongest. Structural equation modeling was used to explore the adequacy of a theoretical model linking topophilia and QOL. The model fit the data extremely well: chi2 = 5.02, p = 0.414; correlation = 0.12 (p = 0.047). All four domains of topophilia were significantly correlated with the level of restoration experienced by respondents at their current domicile [for cognitive challenge: r = 0.19; p < 0.01; familiarity: r = 0.12; p < 0.05; synesthetic tendency: r = 0.18; p < 0.01; ecodiversity (the highest value): r = 0.28; p < 0.01]. Within ecodiversity, preferences for water and flowers were associated with high overall QOL (r = 0.162 and 0.105, respectively; p < 0.01 and 0.05, respectively). Within the familiarity domain, identifiability was associated with the environmental domain of QOL (r = 0.115; p < 0.05), but not with overall QOL. These results provide a new methodologic framework for linking environmental quality and human health and for implementing evidence-based provision of restorative environments through targeted design of built environments to enhance human QOL.