Deterioration of cardiac contractility during congestive heart failure (CHF) is believed to involve decreased function of individual cardiomyocytes, and may include reductions in contraction magnitude and/or kinetics. We examined the progression of in vivo and in vitro alterations in contractile function in CHF mice, and investigated underlying alterations in Ca²⁺ homeostasis. Following induction of myocardial infarction (MI), mice with CHF were examined at early (1-week post-MI) and chronic (10-weeks post-MI) stages of disease development. SHAM-operated mice served as controls. Global and local left ventricle function were assessed by echocardiography in sedated animals (~2% isoflurane). Excitation-contraction coupling was examined in cardiomyocytes isolated from the viable septum. CHF progression between 1-week and 10-weeks post-MI resulted in increased mortality, development of hypertrophy, and deterioration of global left ventricular function. Local function in the non-infarcted myocardium also declined, as posterior wall shortening velocity was reduced in chronic CHF (1.2±0.1 cm•s-1 vs. 1.9±0.2 cm•s-1 in SHAM). Parallel alterations occurred in isolated cardiomyocytes as contraction and Ca²⁺ transient time to peak values were prolonged in chronic CHF (115±6%, 158±11% SHAM values, respectively). Surprisingly, contraction and Ca²⁺ transient magnitudes in CHF were larger than SHAM values at both time points, resulting from increased sarcoplasmic reticulum Ca²⁺ content and greater Ca²⁺ influx via L-type channels. We conclude that in mice with CHF following myocardial infarction, declining myocardial function involves slowing of cardiomyocyte contraction without reduction in contraction magnitude. Corresponding alterations in Ca²⁺ transients suggest that slowing of Ca²⁺ release is a critical mediator of CHF progression.