To study the association between postmenopausal hormone therapy (PMH) use and the risk of rheumatoid arthritis (RA) stratifying the cases by the presence/absence of antibodies against citrullinated peptides (ACPA). A subset of the Epidemiological Investigation of RA (EIRA), a population-based case-control study, comprising postmenopausal women aged 50-70 living in Sweden, between 2006 and 2011 was analysed (523 cases and 1057 controls). All participants answered an extensive questionnaire, including questions regarding PMH use and potential confounders (education, smoking, BMI, oral contraceptives, reproductive factors). We calculated odds ratios (OR) of developing ACPA-positive/-negative RA, with 95% confidence intervals (CI) and adjusted for age, residential area and smoking. Current users of PMH had a decreased risk of ACPA-positive RA compared with never users (OR 0.6, 95% CI 0.3-0.9). The decreased risk was observed mainly in the age-group 50-59 years (OR 0.3, 95% CI 0.1-0.8) but not in the age-group 60-70 years (OR 0.8, 95% CI 0.4-1.4). Among current users of a combined therapy (estrogen plus progestogens) an OR of 0.3 (95% CI 0.1-0.7) of ACPA-positive RA was observed, while no significant association was found among women who used estrogen only (OR 0.8, 95% CI 0.5-1.6). No association between PMH use and ACPA-negative RA was found. PMH use might reduce the risk of ACPA-positive RA in post-menopausal women over 50 years of age, but not of ACPA-negative RA. The negative influence of this treatment on the risk of other chronic conditions cannot be overlooked.