Introduction Autoimmune hemolytic anemia (AIHA) is a rare disease characterized by the destruction of red blood cells by warm or cold autoantibodies. Epidemiological data are lacking about AIHA incidence, the prevalence of associated disorders and the risk of death, thrombosis and infection as compared with the general population. This study was designed to answer these questions. Methods Patients were selected from the AHEAD cohort. This cohort is built in the French national health database (named Système national des données de santé, SNDS) linking sociodemographics, out-hospital and hospital data for the entire French population (67 million inhabitants). The AHEAD cohort is the cohort of all incident AIHA in France. Patients were selected between 2012-2017. The date of AIHA diagnosis was defined by the first hospital discharge diagnosis or the first long-term disease (recorded by general practitioners) of AIHA occurring after a prior observation period in the SNDS of at least two years. Patients were identified using the D59.1 code of the international classification of diseases, version 10 (positive predictive value: 90.0%). The incidence of AIHA was calculated in the whole French population, by age, sex and calendar months. Causes of secondary AIHA and Evans syndrome were searched in the year before the diagnosis of AIHA using long-term disease and hospital discharge diagnoses. Each patient was matched to five controls on age and sex from the general population. The follow-up ended on December 31, 2018. One- and five-year cumulative incidences of death, hospitalization for thrombosis and for infection were assessed in AIHA patients and in controls, with their 95% confidence intervals (95% CIs). Results During the study period, 9,663 incident AIHA patients were included. The median age was 69 years and 55.6 of the patients were female. The overall incidence of AIHA was 2.4 per 100,000 person-years (95% CI: 2.4 - 2.5). The incidence of AIHA in women during genital activity (15 - 45 years-old, 1.2 per 100,000 person-years, 95% CI: 1.1 - 1.3) was higher than in males of same age (0.7 per 100,000 person-years, 95% CI: 0.6 - 0.7). The incidence of AIHA was dramatically increased in the elderly (>75 years of age: 10.5 per 100,000 person-years; 95% CI: 10.2 - 10.8) and the very elderly (>90 years of age, 12.1 per 100,000 person-years; 95% CI: 11.1 - 13.2), as compared with people <50 year-old (0.9 per 100,000 person-years; 95% CI: 0.9 - 1.0). Incidences were higher in males than in females in people >65 year-old. This pattern was observed for both primary and secondary AIHA. There were no relevant variations of incidence by calendar months for both primary and secondary AIHA. AIHA was primary in 55.2% of cases, associated with hematological malignancy in 30.2% and with lupus in 5.2%. Evans syndrome accounted for 5.8% of AIHAs. The patients were matched with 47,753 controls. The overall follow-up in the cohort was 28,630 person-years. The 1-year cumulative incidence of death was 18.6% (95% CI: 17.8 - 19.4) in AIHA (in primary AIHA: 16.5%, 95% CI: 15.5 - 17.4), versus 3.1% (95% CI: 3.0 - 3.3) in controls. The 5-year cumulative incidence of death was 36.1% (95% CI: 34.9 - 37.2) in AIHA (in primary AIHA: 32.4%, 95% CI: 30.9 - 33.8) and 15.1% (95% CI: 14.7 - 15.5) in controls. The 1-year cumulative incidence of hospitalization for thrombosis was 6.0% (95% CI: 5.6 - 6.5) in AIHA (in primary AIHA: 5.7%, 95% CI: 5.1 - 6.4) versus 1.8% (95% CI: 1.7 - 1.9) in controls. The 5-year cumulative incidence of hospitalizations for thrombosis was 11.1% (95% CI: 10.4 - 11.8) in AIHA (in primary AIHA: 10.9%, 95% CI: 9.9 - 11.9) versus 7.0% (95% CI: 6.7 - 7.3) in controls. The 1-year cumulative incidence of hospitalization for infection was 22.9% (95% CI: 22.1 - 23.8) in AIHA (in primary AIHA: 20.9%, 95% CI: 19.8 - 22.0) versus 3.5% (95% CI: 3.3 - 3.6) in controls. The 5-year cumulative incidence of hospitalization for infection was 37.5% (95% CI: 36.4 - 38.6) in AIHA (in primary AIHA: 33.7%, 95% CI: 32.2 - 35.1) versus 13.5% (95% CI: 13.1 - 13.9) in controls. Conclusion The incidence of AIHA (primary or secondary) was more than ten times higher in the elderly and very elderly as compared with people <50 year-old, suggesting a potential role for immunosenescence. As compared with the general population, AIHA patients had an increased risk of death, hospitalization for infection and thrombosis. It was similar in primary and secondary AIHA. Disclosures Moulis: Grifols: Research Funding; Amgen: Other: meeting attendance grant; Novartis SAS: Membership on an entity's Board of Directors or advisory committees, Other: meeting attendance grant, Research Funding.