This prospective study was an evolution of a new sensitive creatine kinase (CK) isoenzyme MB immunoassay in 156 patients, admitted consecutively to the coronary care unit, suspected of having acute myocardial infarction (MI), with regard to clinical applicability and clinical outcome. 42% of the patients had MI based on WHO criteria. The remaining 91 patients could be divided into a group with ischemic heart disease (IHD) without MI being present (n = 65) and a group with non-IHD (n = 26). In the former, a subgrouping based on changing CK MB levels (n = 24) or stable CK MB levels (n = 41) as compared to the non-IHD group could be performed. These patients were not diagnosed using the routine diagnostic procedures. Follow-up was carried out for 30 months (median 22). The prognosis as evaluated by cardiac death was significantly better for patients with stable CK MB levels than for those with changing CK MB levels, inasmuch as the cumulative probability not to suffer cardiac death was 95 ± 3 and 66 ± 10% after 2.5 years, respectively (p < 0.003). It was 52 ± 6% for the patients with MI, similar to patients with changing CK MB levels (p = 0.15). We conclude that this new CK MB assay can detect a subgroup of patients with IHD, which is not diagnosed using routine diagnostic procedures, with a poor clinical outcome.