It has been suggested that a decrease in lead impedance may predict pacing lead failure, but there is limited prospective data about the relation of changes in lead impedance over time to lead performance. We monitored changes in lead impedance through implantable pulse generators with real-time telemetry data capability in 105 patients with Medtronic 4012 leads (n = 38) and Medtronic 4004 leads (n = 67). Pacing lead failure was documented by serial ambulatory electrocardiographic monitoring or intensified pacemaker clinic surveillance. A significant decrease in lead impedance was observed in patients with Medtronic 4012 and Medtronic 4004 leads with documented lead failure, whereas lead impedance remained stable over time in patients without documented lead failure. The sensitivity and specificity of a lead impedance decrease of ≥15% to predict lead failure were 69% and 70%, respectively. The sensitivity and specificity of a lead impedance decrease of ≥30% to predict lead failure were 36% and 90%, respectively. The positive and negative predictive values for a lead impedance decrease of ≥15% were 54% and 81%, respectively, and for a lead impedance decrease of ≥30% were 65% and 73%, respectively. Thus, small decreases in lead impedance may identify failing leads. Serial measurement of pacing lead impedance over time is a useful tool to monitor pacing lead performance.