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Background: The minimum variance (MV) beamformer can significantly improve the image resolution in ultrasound imaging, but it has limited performance in noise reduction. We recently proposed the covariance matrix-based statistical beamforming (CMSB) for medical ultrasound imaging to reduce sidelobes and incoherent clutter.Methods: In this paper, we aim to improve the imaging performance of the MV beamformer by introducing a new pixel-based adaptive weighting approach based on CMSB, which is named as covariance matrix-based adaptive weighting (CMSAW). The proposed CMSAW estimates the mean-to-standard-deviation ratio (MSR) of a modified covariance matrix reconstructed by adaptive spatial smoothing, rotary averaging, and diagonal reducing. Moreover, adaptive diagonal reducing based on the aperture coherence is introduced in CMSAW to enhance the performance in speckle preservation.Results: The proposed CMSAW-weighted MV (CMSAW-MV) was validated through simulation, phantom experiments, and in vivo studies. The phantom experimental results show that CMSAW-MV obtains resolution improvement of 21.3% and simultaneously achieves average improvements of 96.4% and 71.8% in average contrast and generalized contrast-to-noise ratio (gCNR) for anechoic cyst, respectively, compared with MV. in vivo studies indicate that CMSAW-MV improves the noise reduction performance of MV beamformer.Conclusion: Simulation, experimental, and in vivo results all show that CMSAW-MV can improve resolution and suppress sidelobes and incoherent clutter and noise. These results demonstrate the effectiveness of CMSAW in improving the imaging performance of MV beamformer. Moreover, the proposed CMSAW with a computational complexity of [Formula: see text] has the potential to be implemented in real time using the graphics processing unit. [ABSTRACT FROM AUTHOR]