Background <p>Mitral regurgitation (MR) is under-diagnosed and under-treated. Point-of-care ultrasound devices now include color Doppler technologies that can enhance the physical exam. Focused handheld imaging protocols might improve detection of mitral regurgitation.</p> Methods <p>Patients were prospectively scanned with a limited protocol using the Butterfly IQ + device at Tufts Medical Center (Boston, MA). Comprehensive staging of MR was done with cart-based transthoracic echocardiography (TTE) during the same encounter. Handheld imaging-based MR severity was assessed by a board certified echocardiographer blinded to the cart-based results. Performance of handheld color Doppler imaging for identifying significant MR was assessed across a range of disease prevalence values.</p> Results <p>100 patients were prospectively scanned, 45% were women. The median age was 75 (IQR 70–80). The Median LVEF was 60 (IQR 54–64%). Overall, 44 (44%) had some degree of MR. 8 (8%) had significant MR, defined as ≥ moderate. The sensitivity of handheld parasternal long axis color Doppler imaging for the detection of ≥ moderate MR was poor (38% 95% CI 8.5% − 75.5%). PPV and NPV ranged from 25% to 60% and 91.9%-98.9%, across a range of potential disease prevalence rates. There was poor agreement between handheld ultrasound and TTE derived MR grade (weighted kappa 0.08, 95% CI -0.01–0.17). There was modest correlation between assigned grades by each imaging method (Spearman <i>r</i> = 0.41, <i>p</i> &lt; 0.001).</p> Conclusions <p>Limited handheld color Doppler imaging has limited value in screening for significant mitral regurgitation. Routine assessment of handheld imaging protocols proposed for cardiac disease detection are needed.</p> Clinical trial number <p>Not applicable.</p>