The prevalence, clinical characteristics, and outcomes of patients with antimitochondrial antibodies (AMAs), but no clinical evidence of primary biliary cholangitis (PBC), are largely unknown. A prospective study of AMA incidence was conducted through a nationwide network of 63 French immunology laboratories. Clinical data from 720 of 1,318 AMApositive patients identified in 1 year were collected. Patients were categorized as either newly diagnosed with PBC (n 5 275), previously diagnosed with PBC (n 5 216), or with nonestablished diagnosis of PBC (n 5 229). The latter group was specifically evaluated. Follow-up data were collected for up to 7 years after detection of AMAs. Prevalence of AMApositive patients without evidence of PBC was 16.1 per 100,000. These patients had the following characteristics: 78% female; median age 58 years; median AMA titer 1:160; extrahepatic autoimmune disorders 46%; normal serum alkaline phosphatases (ALP) 74%; ALP above 1.5 times the upper limit of normal 13%; and cirrhosis 6%. Compared to those newly diagnosed with PBC, the patients were slightly younger, had lower AMA titers, and lower sex-ratio imbalance. Among the patients with normal ALP and no evidence of cirrhosis, the 5-year incidence rate of PBC was 16%. Whereas no patients died from PBC, the 5-year survival rate was 75%, as compared to 90% in a control, standardized population matched for age and sex (P < 0.05). Conclusion: Nearly half of the newly detected AMAs in clinical practice does not lead to a diagnosis of PBC. PBC is unrecognized in 13% of those cases. Only 1 in 6 patients with AMAs and normal ALP will develop PBC after 5 years. The mortality of AMA-positive patients without PBC is increased irrespective of the risk of PBC development.