We assessed incidence, magnitude, and time course of cardiac troponin I (cTnI) increase after pacemaker implantation in patients without acute coronary syndromes (ACSs). Seventy patients (mean age 71 years, interquartile range 44 to 92, 38 men) undergoing elective implantation of a single-/dual-chamber pacemaker with active/passive fixation leads were enrolled, excluding subjects with clinical suspicion of ACS, abnormal basal cTnI level, or presenting conditions predisposing to abnormal cTnI. Cardiac TnI concentrations were determined in basal conditions, at the end of the procedure, and after 8, 12, and 24 hours. Single-/dual-chamber devices were implanted in 31 of 39 patients. Cardiac TnI peak concentration occurred within the 12-hour assay in 69 of 70 patients; 26 of 70 had a cTnI above the normal cut-off range. All patients presented normal cTnI at 24-hour assay. In conclusion, pacemaker implantation is associated with increases of cTnI levels in up to 37% of patients. This can affect the specificity of cTnI assessment for ruling out ACS, especially within 12 hours after the procedure. These data deserve consideration in a contemporary setting, in which troponin has gathered a pivotal role in the diagnosis and therapy of ACS, and in particular clinical presentations in which electrocardiogram loses its diagnostic capabilities (due to paced rhythms) and symptoms may be lacking or confusing.