Abstract Mean scatterer spacing (MSS) is a quantitative signature for disease diagnosis and tissue characterization. However, it is difficult to objectively extract the coherent components from the ultrasound RF echo signals to improve the accuracy performance of the MSS estimation. In the present study, a novel MSS estimation method with the matched Gabor atoms selected based on Nakagami parameters is proposed. Firstly, the ultrasound signals are decomposed into a series of Gabor atoms, and the envelopes of the residual signals are fitted with the Nakagami distribution. Then, the second order difference (SOD) of the shape parameters in Nakagami distribution is calculated to select the optimal atoms to match the coherent components. Finally, the locations of the selected Gabor atoms are used to estimate the MSS. In order to evaluate the performance of the proposed method, the simulated RF echo signals are modelled based on four regular degrees of the scatterer distributions, and then the optimally matched atoms are selected to estimate MSSs. The results based on simulated signals demonstrate that the propose method can provide accurate MSS estimation, which are advantageous for improving quantitative diagnosis of diseases and tissue characterization