Abstract This study assessed the flexural and fatigue strength of the 3D-printed polylactic acid (PLA) samples across diverse printing designs and parameters. The experiment setup included different layer heights, first layer thicknesses, infill densities, top/bottom infill patterns, extruder temperatures, perimeters, and different types of solid layer top and bottom. Our findings suggest that the fatigue strength of PLA printing specimens is more significantly influenced by an increase in the thickness of the first layer compared to flexural strength. Specifically, the rate of increase in bending strength is lower in cases of layer height and initial layer height in contrast with other factors. Notably, specimens with an initial layer thickness of 0.4 mm reached the highest number of cycles until failure, recording 21022 cycles. Furthermore, the study identifies the infill pattern's impact on strength, highlighting that the line infill pattern type case has the highest bending strength of 75.97 Mpa and surpasses the honeycomb pattern in bending strength. Compared to the Honeycomb pattern, the rectilinear design has 2.1% higher bending strength. The number of cycles to failure of the rectilinear pattern is greater than those of the honeycomb pattern. In comparison to other patterns, the Rectilinear Top/Bottom infill pattern has a higher interest rate of 27.5% for bending strength and 200.83% for fatigue strength. Additionally, greater bending and flexural strength are obtained by raising the solid layer top, bottom, and perimeter values, respectively. In comparison to the other temperatures, the bending strength and fatigue strength are highest at 200°C. Therefore, the first layer height of 0.4 mm, the top/bottom rectilinear infill pattern, the extruder temperature of 200 °C, the perimeter value of 3, the solid layer/top value of 3, and the solid layer/bottom value of 3 are the optimal values for the part subjected to at the same time bending strength combined with fatigue strength. This study may provide an overview of bending and fatigue strength in connection to printing design and printing parameters, as well as the ideal parameters for 3D printing with the PLA material.