Microfluidic mixers with twisted geometries show promise for high mixing efficiency, especially at elevated flow rates. However, there is a lack of understanding regarding the optimal geometrical parameters to enhance mixing across various Reynolds numbers. This study aimed to explore the influence of pitch number, cross-section geometry, and eccentricity ratio on the performance of the twisted micromixer. The flow field in these micromixers was solved numerically and the mixing index and pressure drop were calculated for Reynolds numbers of 1 to 400. Twisted micromixers with rectangular cross-sections and aspect ratios of 0.5 and 2 outperformed those with square cross-sections by up to 34% in mixing efficiency, exceeding 90% efficiency for Reynolds numbers from 1 to 400. Moreover, the eccentricity ratio (ER) was studied for the first time in twisted micromixers in this study and demonstrated a critical role in improving the mixing performance. For low to intermediate Reynolds numbers, the highest ER of 0.75 showed the best performance, while for high Reynolds numbers, an ER of 0.5 was optimal. These insights offer valuable direction for designing high-performance micromixers for advanced microfluidic systems.