BACKGROUND Angiotensin-converting enzyme (ACE) inhibitors are associated with an increased risk of angioedema, but the risk of recurrent angioedema if treatment is continued is not known. OBJECTIVE To test the hypothesis that the association between ACE inhibitor use and angioedema may not be recognized and to determine characteristics of angioedema associated with continued use of ACE inhibitors. METHODS Retrospective cohort study. METHODS Tennessee Medicaid program. METHODS Medicaid enrollees aged 15 years or older who used an ACE inhibitor and had a first documented episode of angioedema between 1986 and 1992 were followed up for recurrent episodes through June 1993. RESULTS We previously identified 82 patients with a first confirmed diagnosis of angioedema during 51 752 person-years of ACE inhibitor use in this population (1.6 per 1000 person-years). Among these 82 patients, there were 16 outpatient recurrences of angioedema among 13 patients during 189 patient-years of follow-up (8.5 per 100 patient-years). The rate of angioedema was much higher in users of ACE inhibitors with continued exposure (18.7 per 100 patient-years) than in those whose use of the drug was discontinued (1.8 per 100 patient-years) (P=.001). Review of the medical records for patients taking ACE inhibitors who had recurrent angioedema revealed that physicians attributed angioedema to a number of causes not related to ACE inhibitor use, even after multiple recurrences. CONCLUSIONS Continuing use of ACE inhibitors in spite of angioedema results in a markedly increased rate of angioedema recurrence with serious morbidity.