BACKGROUND: There is increasing concern about the potential effects of the lipodystrophy syndrome on the health and quality of life of HIV-infected patients. OBJECTIVE: Understand patients’ perception of the significance of the lipodystrophy syndrome's quality-of-life effects. DESIGN: Cross-sectional study of volunteer HIV-infected patients. SETTING: An urban, university-affiliated HIV clinic in San Diego, California. Patients: 75 well-educated, predominantly male HIV-infected patients. MEASUREMENTS: Patients' beliefs about the importance of appearance upon quality of life and preferences for hypothetical states performed using the standard gamble and time trade-off methods. RESULTS: Almost all patients (95%) indicated that appearance was important to their quality of life, and 89% agreed that they would be "really bothered" if their HIV diagnosis were revealed by their appearance. Patients were willing, on average, to give up 2 years (s.d. 2.8), out of a 10-year life-expectancy, to live in good health rather than live with the syndrome, over and above what they would give up to be free of symptoms from HIV infection. Patients would take an additional 13% (s.d. 20%) risk of death to be cured of HIV infection when complicated by the syndrome (median increase in risk, 9%), above the risk they would accept to be cured of uncomplicated HIV infection. The amount that the patients would trade off was associated with beliefs about the importance of their appearance to quality of life (p=0.0045) and worry that their appearance would expose their diagnosis by (p=0.032). CONCLUSIONS: The physical effects of the lipodystrophy syndrome are important enough to cause many patients to consider accepting considerable risks of death or trading off substantial life-expectancy to avoid the syndrome. Physicians may need to tailor HIV care to this aspect of patients’ preferences.