Limited evidence suggests that autoimmune diseases tend to co-occur, although data are needed to determine whether individuals with an existing autoimmune disorder are at increased risk of a second disorder. The authors conducted a series of population-based cohort studies, utilizing the United Kingdom General Practice Research Database, to assess intraindividual risks of coexistence of rheumatoid arthritis (RA), autoimmune thyroiditis (AIT), multiple sclerosis (MS), and insulin-dependent diabetes mellitus (IDDM) during 1990-1999. Sex-specific age- and calendar-period standardized incidence ratios (SIRs) were calculated for development of a second autoimmune disease among index populations including 22,888 RA, 26,198 AIT, 4,332 MS, and 6,170 IDDM patients compared with the general population. Among those with IDDM, adjusted AIT rates were higher than expected for both males (SIR = 646.0, 95% confidence interval (CI): 466, 873) and females (SIR = 409.6, 95% CI: 343, 485), as were RA rates for females (SIR = 181.6, 95% CI: 136, 238). Coexistence of AIT and RA was also shown for either disease sequence (sex-specific SIRs = 130.4-162.0). However, point estimates suggested an inverse relation between RA and MS, irrespective of diagnostic sequence. This study demonstrates coexistence of RA, AIT, and IDDM at higher than expected rates but reduced comorbidity between RA and MS.