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• Main and interaction effects of printing parameters on the mechanical properties of 3D printed samples. • Failure mode analysis of fractured samples. • Fractographic features analysis according to printing parameters. • Relationship between the plastic deformation and the printing parameters. Predicting the mechanical properties or analyzing the failure mode of fused deposition modeling products is challenging due to the layer-by-layer structure and the manufacturing parameters that can interact and be potentially conflicting. Understanding the effects and potential interactions of printing parameters, such as layer thickness, printing (build) orientation, infill density, and infill pattern, is crucial to enhancing the performance of in-service parts. This study investigates the main and interaction effects of layer thickness and printing orientation on the mechanical and failure properties in the case of two levels of infill density (100% and 40%). Tensile tests on 3D Printed PLA samples were carried out for this purpose. An ANOVA analysis was performed based on the experimental results to examine these effects on the mechanical properties. The primary findings demonstrate that the selected parameters' main and interaction effects vary throughout the considered infill densities. With this variation, it is clearly stated that samples with a 100% infill density are more sensitive to interaction effects, and the ones with a 40% infill density are more sensitive to main effects. Examining the fracture surface also details the fractographic features linked to the printing parameters, such as the appearance of plastic deformation and inter-filament debonding. [ABSTRACT FROM AUTHOR]