We evaluated the robustness of an accelerated and optimized diffusion-weighted sequence using the simultaneous-multislice (SMS) technique for scan time reduction and a 3D Diagonal diffusion mode to optimize image quality in clinical routine. 152 patients received clinically indicated abdominal MRI including the optimized diffusion-weighted sequence (DWIOPT). A subgroup of 41 patients additionally received a standard diffusion-weighted sequence (DWISTD) as reference. Qualitative and quantitative image parameters were evaluated. In the interindividual comparison, DWIOPT proved equal to superior to DWISTD with comparable ADC-values. In the patients receiving DWIOPT only, image quality maintained substantial proving constant and stable results in a large cohort.