Pompe’s disease is an autosomal recessive and often fatal condition, caused by mutations in the acid α-glucosidase gene, leading to lysosomal glycogen storage in heart and skeletal muscle. We investigated the cardiac phenotype of an acid α-glucosidase knockout (KO) mouse model. Left ventricular weight-to-body weight ratios were increased 6.3 ± 0.8 mg/g in seven KO compared with 3.2 ± 0.2 mg/g in eight wild-type (WT) mice (P < 0.05). Echocardiography under ketamine-xylazine anesthesia revealed an increased left ventricular (LV) wall thickness (2.17 ± 0.16 in KO vs. 1.18 ± 0.10 mm in WT mice, P < 0.05) and a decreased LV lumen diameter (2.50 ± 0.32 in KO vs. 3.21 ± 0.14 mm in WT mice, P < 0.05), but LV diameter shortening was not different between KO and WT mice. The maximum rate of rise of left ventricular pressure (LV dP/dt_max) was lower in KO than in WT mice under basal conditions (2,720 ± 580 vs. 4,440 ± 440 mmHg/s) and during dobutamine infusion (6,220 ± 800 vs. 8,730 ± 790 mmHg/s, both P < 0.05). Similarly, during isoflurane anesthesia LV dP/dt_max was lower in KO than in WT mice under basal conditions (5,400 ± 670 vs. 8,250 ± 710 mmHg/s) and during norepinephrine infusion (10,010 ± 1,320 vs. 14,710 ± 220 mmHg/s, both P < 0.05). In conclusion, the markedly increased LV weight and wall thickness, the encroachment of the LV lumen, and LV dysfunction reflect cardiac abnormalities, although not as overt as in humans, of human infantile Pompe’s disease and make these mice a suitable model for further investigation of pathophysiology and of novel therapies of Pompe’s disease.