<p>This meta-analysis aimed to assess the efficacy of stem cell therapy using medical imaging modalities, namely myocardial perfusion scanning with Technetium (Tc)-99&#xa0;m methoxy isobutyl isonitrile (MIBI) using single-photon emission computed tomography (SPECT), compared with cardiac magnetic resonance imaging (MRI) to test in the initial treatment of patients with ischemic heart failure (IHF) and acute myocardial infarction (AMI). Major databases were searched from January 1980 to Feb 2025 using MeSH standardized keywords to find relevant articles. A total of 63 randomized controlled trials were included in the meta-analysis, including 2,651 patients with AMI or IHF who underwent stem cell therapy, and 2,213 people as controls. The results showed that the highest significant increase of left ventricular ejection fraction was 0.66% (95%CI: 0.02, 0.34; <i>I</i>^<i>2</i>: 93%, <i>P</i> = 0.002) in stem cell therapy, when using SPECT compared with Echo. We found that the highest significant decrease of left ventricular end-systolic volum was − 0.32%mL (95%CI: -0.51, -0.13; <i>I</i>^<i>2</i>: 71%, <i>P</i> = 0.001) in stem cell therapy, when using MRI compared with echocardiography (Echo). We found that the highest significant decrease of left ventricular end-diastolic volume was − 0.27%mL (95%CI: -0.47, -0.06; <i>I</i>^<i>2</i>: 73%, <i>P</i> = 0.010) in stem cell therapy, when using MRI compared with Echo. We observed that the highest significant decrease of infract size was − 0.36%mL (95%CI: -0.70, -0.02; <i>I</i>^<i>2</i>: 79%, <i>P</i> = 0.04) in stem cell therapy, when using MRI compared with Echo. Since SPECT and MRI have a superior diagnostic value than Echo in assessing the efficacy of stem cell therapy in cardiovascular disease (CVD), it is recommended that they be considered as the first measure for novel treatment assessment in patients with CVD.</p>