Objective. To measure the perception of quality of life in Venezuelan patients with knee osteoarthritis and to identify those variables that may influence it. Methods. A multicenter, cross-sectional study of 126 mestizo patients with knee osteoarthritis recruited from 8 rheumatology centers in Venezuela. We used a Spanish-translated version of the Arthritis Impact Measurement Scales (AIMS), as adapted in Venezuela. One-way analysis of variance was used to compare the AIMS mean total score among subgroups of knee pain, anatomic stage, and socioeconomic status (SES); a post-hoc test was performed to identify significant intragroup differences. Pearson's correlation coefficient was used to examine correlations between age, body mass index (BMI), disease duration, knee pain, and AIMS score. Associations between radiologic stage, SES, and AIMS scores were examined using Spearman's rank correlation. Multiple regression analysis was used to estimate predictor factors of AIMS scores. Results. A significant correlation was found between total AIMS scores and knee pain, age, and socioeconomic status, but not with BMI, disease duration, or anatomic stage. Patients with severe knee pain differed from those with mild and moderate pain, and the highest AIMS mean total score was seen in patients within the severe knee pain subset. Patients in the highest socioeconomic levels differed from those within lowest categories. Patients classified as being at the levels of relative and critical poverty showed the highest AIMS scores. Multiple regression analysis showed that knee pain was the only variable that exerted an independent effect on the quality of life in our patients. Conclusion. The perception of quality of life is negatively affected by increasing levels of joint pain, old age, and low socioeconomic status in Venezuelan patients with knee osteoarthritis. Our study supports the need for an early and vigorous approach to treat pain in this group of patients.