Purpose <p>A newer design of crowns known as Endocrowns was introduced for endodontically treated teeth. The aim of this in vitro study was to compare fracture resistance and failure modes of two margin preparation for computer-aided design/computer-aided manufacturing (CAD-CAM) fabricated polymethyl methacrylate (PMMA) endocrowns for primary molars.</p> Methods <p>Twenty extracted human primary molars were pulpectomized and restored with composite resin as per the standard protocol. Half the samples were prepared for endocrown with butt margin whilst the other half were given shoulder margin. The prepared teeth were scanned using a CADCAM scanner, and endocrowns were fabricated, cemented using glass ionomer luting cement, and subjected to thermocycling and chewing simulations. Samples were subjected to fracture resistance (FR) test using a universal testing machine and failure modes were assessed. Data were analysed using the Kruskal–Wallis and Chi-square test.</p> Results <p>Mean FR was 1230.6 ± 305.4 N for butt-margin endocrowns and 1355.1 ± 293.9 N in shoulder margin design (<i>p</i> = 0.08). For the failure mode, most samples showed less than half of the crown lost (Class II) in Group 1 and severe fracture of the crown or tooth (Class V) in Group 2. However, there was no statistically significant difference between the two designs of endocrowns (<i>p</i> = 0.91) for the failure modes.</p> Conclusions <p>The study concluded that the margin designs did not affect the fracture resistance and the failure modes of the PMMA endocrowns in primary molars. In vivo studies are needed to ascertain the long-term efficacy of PMMA endocrowns in endodontically treated primary molars.</p>