In conventional extrusion-based three-dimensional (3D) printing (E3DP), smaller needles reduce cell viability due to increased fluid forces like pressure and shear stress. A novel E3DP approach has emerged, involving 3D printing with structured inks. Fluid forces in both conventional and structured ink-based methods were evaluated through computational fluid dynamics (CFD) simulations. By employing 18G needles, we showcased the advantages of structured inks, including 2-symmetric, 4-symmetric, vascular-like, and hepatic lobule analogue-like inks, which demonstrated consistently lower pressures and shear stress compared with conventional inks. Specifically, vascular-like inks with a 2:1:1 extruded fiber layer distance showed significantly lower shear stress (average 6.595e+0 Pa, maximum 2.069e+2 Pa) than conventional methods. Equivalent analyses explored commonly used symmetric and core–shell inks, examining fluid forces on cells. Particularly, in core–shell inks with a 2.8 mm core layer radius, cells in the flow domain of the shell layer experienced an equivalent viscosity of 3.70 Pa·s, while in the core layer, it was 1.72 Pa·s. The analyses revealed a positive correlation between equivalent homogeneous ink viscosity and shear stress. The proposed workflow, emphasizing cell viability, offers an efficient approach for structured ink design. Also, experiments that used vascular-like ink-based printing as an example indicated significantly higher cell viability when compared with conventional printing. This research provides valuable insights for enhancing cell viability in 3D printing and advancing printing material design.