Objective. To assess the impact of gout on health-related quality of life (HRQoL) among patients in three large US cities. Methods. Gout patients completed the Short Form-36 (SF-36) and a series of questions regarding their gout, comorbidities and demographics. Their physicians confirmed the gout diagnosis and evaluated the severity of patient's gout. The differences in mean norm-based SF-36 scores between the US norms and gout patients and between subgroups of gout patients were calculated. The relative weight and significance of gout-related characteristics associated with patients' HRQoL were also calculated. Results. The majority of the patients were males with a mean age of 62.2 years and median disease duration of 13.8 years. Most were overweight/ obese with several comorbidities. Half of the patients experienced three or more gout attacks per year with a typical gout attack involving five joints and lasting for at least 4 days. The Physical Component Summary (PCS) and Mental Component Summary (MCS) was significantly lower for gout patients (P < 0.002 and P < 0.001, respectively). Among gout patients, the mean PCS and MCS were lower for those with more frequent gout attacks and greater number of affected joints (P < 0.005 and P < 0.001, respectively). After adjusting for age, gender and comorbidities, the number of joints involved during a typical and the worst gout attack had the greatest impact on patient's PCS and MCS. Conclusion. Gout patients had clinically significant lower HRQoL than their age-matched US norm. Comorbidities and several additional gout-related factors significantly impacted the overall HRQoL. © The Author 2009. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.