To work efficiently in healthcare organizations and optimize resources, team members should agree with their leader's decisions critically. However, nowadays, little evidence is available in the literature. This systematic review and meta-analysis has assessed the effectiveness of leadership interventions in improving healthcare outcomes such as performance and guidelines adherence. Overall, the search strategies retrieved 3,155 records, and 21 of them were included in the meta-analysis. Two databases were used for manuscript research: PubMed and Scopus. On 16th December 2019 the researchers searched for articles published in the English language from 2015 to 2019. Considering the study designs, the pooled leadership effectiveness was 14.0% (95%CI 10.0-18.0%) in before-after studies, whereas the correlation coefficient between leadership interventions and healthcare outcomes was 0.22 (95%CI 0.15-0.28) in the cross-sectional studies. The multi-regression analysis in the cross-sectional studies showed a higher leadership effectiveness in South America (beta = 0.56; 95%CI 0.13, 0.99), in private hospitals (beta = 0.60; 95%CI 0.14, 1.06), and in medical specialty (beta = 0.28; 95%CI 0.02, 0.54). These results encourage the improvement of leadership culture to increase performance and guideline adherence in healthcare settings. To reach this purpose, it would be useful to introduce a leadership curriculum following undergraduate medical courses.