OBJECTIVES: The study objectives were to compare long term medication adherence among first time adalimumab and etanercept users over a three-year follow up period, and to identify factors that were associated with high medication adherence. METHODS: A total of 1672 adult (≥ 18 years) rheumatoid arthritis (RA) patients who were first time adalimumab (N=382) or etanercept (N=1290) users between January 1, 2003 and December 31, 2007 in the Kaiser Permanente Southern California (KPSC) Health Plan were included. Subjects were required to have at least two RA diagnosis records and disease-modifying anti-rheumatic drugs (DMARDs) use within one year after the first diagnosis. Continuous enrollment one year prior, and three years after the initiation (index date) of adalimumab and etanercept treatment was required. First time users were defined as subjects who did not use adalimumab or etanercept in the 12-month period prior to index date. Medication adherence was measured through proportion days covered (PDC). Association of long term high adherence with age, gender, race, insurance type, comorbidity and history of oral DMARDs were estimated using Poisson regression with robust standard errors.   RESULTS: The mean age, gender and race distribution were 52.5 years old, 80.4% female, and 34.0% non-whites in adalimumab group; 53.3 years old, 77.9% female, and 36.2% non-whites in etanercept group. The adherence rate in one-year, two-year and three-year follow up in adalimumab group was 0.63, 0.52 and 0.46, and in etanercept group was 0.69, 0.59 and 0.53. The incidence rate ratio (IRR) of adalimumab was 0.78 (95% CI: 0.68 -0.90), 0.73 (95% CI: 0.61-0.88), and 0.70 (95% CI: 0.56-0.87) in one-year, two-year and three-year follow up respectively. Age and history of oral DMARDs were significantly associated with adherence. CONCLUSIONS: This study highlighted a relatively lower long term adherence rate in adalimumab users as compared to etanercept users in adult RA patients within KPSC.