OBJECTIVE: To determine the prevalence of and factors associated with defaulting from antiretroviral treatment (ART) in Jimma, Ethiopia. METHODS: Unmatched case control study: cases were individuals who had missed two or more clinical appointments (i.e. had not been seen for the last 2 months) between January 2005 and February 2007; controls were individuals who had been on ART at least for 1 year and were rated as excellent adherers by the providers. Data were collected from patient records, and by telephone call and home visit to identify the reason for defaulting. RESULTS: Of 1270 patients who started ART, 915 (72.0%) were active ART users and 355 (28.0%) had missed two or more clinical appointments. The latter comprised 173 (13.6%) defaulters, 101 (8.0%) who transferred out, 75 (5.9%) who died, and 6 (0.5%) who restarted ART. Reasons for defaulting were unclear in most cases. Reasons given were loss of hope in medication, lack of food, mental illness, holy water, no money for transport, and other illnesses. Tracing was not successful because of incorrect address on the register in 61.6% of the cases. Taking hard drugs (cocaine, cannabis and IV drugs), excessive alcohol consumption, being bedridden, living outside Jimma town and having an HIV negative or unknown HIV status partner were associated with defaulting ART. CONCLUSION: A significant proportion of patients defaulted from ART treatment. ART clinics should ensure that patients' addresses are correct and complete. Programmatic and counseling efforts to decrease ART defaulting should address illicit drug and excessive alcohol use, decentralise ART services, institute home-based treatment options for seriously ill and bedridden patients, and address patients concerns.