Augmented and slowed late Na⁺ current (I_NaL) is implicated in action potential duration variability, early afterdepolarizations, and abnormal Ca²⁺ handling in human and canine failing myocardium. Our objective was to study I_NaL modulation by cytosolic Ca²⁺ concentration ([Ca²⁺]_i) in normal and failing ventricular myocytes. Chronic heart failure was produced in 10 dogs by multiple sequential coronary artery microembolizations; 6 normal dogs served as a control. I_NaL fine structure was measured by whole cell patch clamp in ventricular myocytes and approximated by a sum of fast and slow exponentials produced by burst and late scattered modes of Na⁺ channel gating, respectively. I_NaL greatly enhanced as [Ca²⁺]_i increased from “Ca²⁺ free” to 1 μM: its maximum density increased, decay of both exponentials slowed, and the steady-state inactivation (SSI) curve shifted toward more positive potentials. Testing the inhibition of CaMKII and CaM revealed similarities and differences of I_NaL modulation in failing vs. normal myocytes. Similarities include the following: 1) CaMKII slows I_NaL decay and decreases the amplitude of fast exponentials, and 2) Ca²⁺ shifts SSI rightward. Differences include the following: 1) slowing of I_NaL by CaMKII is greater, 2) CaM shifts SSI leftward, and 3) Ca²⁺ increases the amplitude of slow exponentials. We conclude that Ca²⁺/CaM/CaMKII signaling increases I_NaL and Na⁺ influx in both normal and failing myocytes by slowing inactivation kinetics and shifting SSI. This Na⁺ influx provides a novel Ca²⁺ positive feedback mechanism (via Na⁺/Ca²⁺ exchanger), enhancing contractions at higher beating rates but worsening cardiomyocyte contractile and electrical performance in conditions of poor Ca²⁺ handling in heart failure.