BACKGROUND A review by the Institute of Medicine found a possible relationship between rubella vaccination and chronic arthritis among women. OBJECTIVE To evaluate the risk of persistent joint and neurologic symptoms in rubella seronegative women subsequently vaccinated with RA 27/3 rubella vaccine. METHODS Retrospective cohort study based on computerized laboratory data and medical record review. Records were reviewed for symptoms occurring within 2 years before and after the date of serological testing and to identify vaccinees. Possible cases were evaluated by a rheumatologist blinded to serological findings and vaccination status. METHODS Large health maintenance organization in northern California. METHODS Women aged 15 to 59 years serotested for rubella during 1990 with continuous health plan membership for 2 years before and after the date of their serological test. Seronegative women immunized within 1 year of serotesting (n=971) were defined as exposed. Primary comparison groups included all unvaccinated, seronegative women (n=924) and randomly selected seropositive, unvaccinated women (n=2421) matched to exposed subjects on serological test date and age (+/-3 years). METHODS Prevalence and incidence of chronic joint and neurologic symptoms during 1-year follow-up period stratified by age and serological findings, immunization, and postpartum status. RESULTS No significantly increased risk was associated with receipt of rubella vaccine for any outcome except for prevalence of carpal tunnel syndrome in vaccinated women at least 30 years old compared with seropositive, unvaccinated women (2.9% vs 1.4%; P=.03). A total of 34 women had onset of conditions within the 1-year follow-up period; 9 of these were in the group of seronegative, immunized women, of whom 6 had onset of symptoms within 6 weeks of vaccination. Among these 6 women, symptoms included transient arthritis or arthralgias (<6 weeks duration) in 4 women, arthralgia of indeterminate chronicity in 1 woman, and carpal tunnel syndrome in 1 woman. Postpartum women across all groups were less likely to be seen for nontraumatic arthropathies than nonpostpartum women (4.5% vs 7.2%, P=.08 in vaccinated women; 4.8% vs 8.1%, P=.09 in seronegative controls; and 4.8% vs 10.0%, P=.01 in seropositive controls). CONCLUSIONS In this large retrospective cohort analysis there was no evidence of any increased risk of new onset chronic arthropathies or neurologic conditions in women receiving the RA 27/3 rubella vaccine. These data support the continued vaccination of rubella-susceptible women to reduce the risk of congenital rubella syndrome.