Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily affects joints with some extraarticular involvement. If inappropriately treated, it usually results in persistent joint pain, irreversible deformities, and functional disability, leading to poor quality of life. Our objective was to evaluate health-related quality of life (HRQoL) and related factors in patients with RA. Four hundred sixty-four patients from the Rheumatoid Arthritis registries of Siriraj and Phramongkutklao teaching hospitals were enrolled. Sociodemographic, clinical and laboratory data related to disease activity, and functional status were collected. HRQoL was assessed using the Thai version of EuroQol five dimensional questionnaire (EQ-5D) and EQ global health visual analogue scale (EQ VAS). Univariate and multivariate analyses were employed to identify factors related to HRQoL. Eighty-five percent were female with a mean age ± SD of 59.15 ± 11.43 years and a mean disease duration ± SD of 11.53 ± 8.3 years. The mean educational level ± SD was 9.42 ± 5.21 years. Almost half were unemployed or retired (47%). They had moderate disease activity (mean cumulative DAS28 ± SD, 3.5 ± 0.8) and mild functional impairment (mean HAQ ± SD, 0.70 ± 0.68). The mean EQ-5D ± SD (0–1) was 0.87 ± 0.13 and mean EQ VAS ± SD (0–10) was 7.94 ± 1.7. Based on the EQ-5D domain, 49% reported that they had no problem with mobility, 83% had no difficulties with self-care, 65% had no difficulties with usual activity, 30% had no pain or discomfort, and 61% had no depression or anxiety. The relationship between problems of each dimension in EQ-5D significantly increased according to severity of RA assessed by the Disease Activity Score (DAS) 28 and Health Assessment Questionnaire (HAQ) (p < 0.01). In multivariate analyses, high cumulative disease activity, functional disability, depression, and anxiety were negatively associated with EQ-5D (adjusted R2 0.38, p < 0.001) and EQ VAS (adjusted R 2 0.19, p < 0.001). Disease severity and psychological disturbance have a negative impact on quality of life in patients with RA. These factors should be considered in management of RA patients to improve the standard of care.