Abstract Paper aims Based on challenges faced in real SPC application, this paper considers implementation and performance of self-starting methodology in multivariate process monitoring. Originality Traditional omnibus charts depend on in-control process parameters while parameters are generally known. However, in real settings, this information may not exist. This paper proposes and compares novel methods to overcome this difficulty. Research method This paper introduces, evaluates the performance and implements multivariate self-starting charts (SSMEC, SSMELR, and SSMME) for multivariate process monitoring. Main findings Proposed SSMME chart is the best choice in real application because it proves better performance in response to various simulation scenarios and gives diagnostic tools for further analysis. Implications for theory and practice The main contributions are the comparison of different self-starting approaches and introducing a novel multivariate self-starting chart that are suitable in real process monitoring and illustrate the benefit of the selected SPC chart with hypertension monitoring.