There is uncertainty as to the comparative prognostic value between cardiac troponin I (cTnI) and CK-MB in acute coronary syndrome (ACS). The objective is to compare the prognostic value between cTnI and CK-MB mass in patients with ACS without ST-segment elevation. Total 127 patients were analyzed in a prospective way in a tertiary cardiology center. Combinations of biomarkers were examined: normal cTnI, normal CK-MB mass (65.5%), normal cTnI, elevated CK-MB mass (3.9%), elevated cTnI, normal CK-MB mass (8.8%), elevated cTnI, elevated CK-MB mass (20.7%). A multivariate analysis of clinical, electrocardiographic and laboratory variables determined the independent prognostic value of biomarkers for the event of death or (re)infarction within 30 days. Patients with at least one elevated biomarker were older (p = 0.02) and males (p < 0.001). The previous use of aspirin (p = 0.001), betablockers (p = 0.003) or statin (p = 0.013) was most frequent among those without elevated cTnI. Patients with both biomarkers elevated had more ST-segment depression (p < 0.001) or elevated creatinine (p < 0.001). In a multivariate analysis with the inclusion of cTnI, the CK-MB mass was not an independent variable for the event of death or (re) infarction within 30 days (odds ratio [OR] 1.16, p = 0.71). When cTnI was not included, we had the following values: age (OR 1.07; p < 0.001); male (OR 1.09; p = 0.77); diabetes mellitus (OR 1.95; p = 0.02); previous stroke (OR 3.21; p =0.008); creatinine level (OR 1.63; p = 0.002); CK-MB mass (OR 1.96; p = 0.03). C-statistic 0.77 (p < 0.001). With a dose of cTnI, CK-MB mass may be dispensable for prognostic evaluation. If cTnI is unavailable, CK- MB mass is acceptable for making a decision on treatment options.