Accurate characterization of tissue pathologies using ultrasonic attenuation is strongly dependent on the accuracy of the algorithm that is used to obtain the attenuation coefficient estimates. In this paper, computer simulations were used to compare the accuracy and the precision of the three methods that are commonly used to estimate the local ultrasonic attenuation within a region of interest (ROI) in tissue; namely, the spectral log difference method, the spectral difference method, and the hybrid method. The effects of the inhomgeneities within the ROI on the accuracy of the three algorithms were studied, and the optimal ROI size (the number of independent echoes laterally and the number of pulse lengths axially) was quantified for each method. The three algorithms were tested for when the ROI was homogeneous, the ROI had variations in scatterer number density, and the ROI had variations in effective scatterer size. The results showed that when the ROI was homogeneous, the spectral difference method had the highest accuracy and precision followed by the spectral log difference method and the hybrid method, respectively. Also, when the scatterer number density varied, the spectral difference method completely failed, while the log difference method and hybrid method still gave good results. Lastly, when the scatterer size varied, all of the methods failed.