Background: Shortness of breath (SOB) is common among healthy women with normal pregnancies. However, when no overt cardiac or extra cardiac etiology is found, a subtle cardiac source must be excluded. Hypothesis: Pregnancy may induce or unmask myocardial dysfunction that may cause SOB. Methods: Healthy pregnant women with significant SOB were recruited for this study. We performed a comprehensive echocardiographic assessment including tissue Doppler imaging (TDI) and 2-dimensional strain imaging (2DS). The echocardiographic data obtained were compared with that of a control group of pregnant women without SOB. Results: Thirty pregnant women with SOB were enrolled in the study (age, 31.8 ± 4.9 years, and gestation, 38.2 ± 2.8 weeks) for whom no overt etiology for SOB was detected. Patients with SOB compared with controls had thicker hearts (septum: 10.1 ± 1.1 vs 8.9 ± 0.9 mm; P < 0.001; posterior wall: 9.4 ± 1.1 vs 8.9 ± 0.9 mm; P < 0.01), shorter E-wave deceleration time (158.0 ± 50.1 vs 187.1 ± 37.6 msec; P = 0.01), and higher pulmonary artery pressure (26.8 ± 6.2 vs 19.0 ± 6.5 mm Hg, P < 0.01). Women with SOB tended to have a lower S' velocity TDI (P = 0.05) and a trend toward increased torsion on 2DS (P = 0.09). Conclusions: Significant SOB during otherwise normal pregnancy is associated with significant echocardiographic findings that may suggest a subtle cardiac involvement. Further investigation is necessary to verify such an association, which may have therapeutic implications for treating SOB of pregnancy.