Objectives <p>To evaluate the effects of cusp reduction and different quartz fiber-ribbon placement strategies on the fracture resistance of endodontically treated maxillary first premolars with mesio-occlusal (MO) cavities.</p> Materials and methods <p>Flexural strength was measured in composite resin and fiber-reinforced composite resin blocks. Finite element analysis (FEA) was performed to compare five restorative designs (EC, FC, CEC, CBFC, and CCFC) in the endodontically treated first premolar. Fracture strength of the repaired extracted teeth were also conducted, fracture loads and failure modes were recorded. One-way ANOVA and Chi-square tests were used (α = 0.05).</p> Results <p>Quartz fiber reinforcement significantly increased flexural strength compared with composite resin alone (<i>P</i> &lt; 0.05). FEA showed that the cusp-reduced restoration with coronal fiber placement generated the lowest cervical stress concentration, whereas the composite-only design showed the highest. In fracture testing, the cusp-reduced restoration with coronal fiber placement exhibited the highest fracture load and was significantly stronger than all other groups (<i>P</i> &lt; 0.05). More non-repairable fractures were observed in the cusp-reduced composite-only and basal-fiber groups.</p> Conclusions <p>Cusp reduction combined with coronal quartz fiber-ribbon placement provided the most favorable biomechanical behavior and the highest fracture resistance.</p> Clinical relevance <p>Premolars with single-wall defects are at relatively high risk of fracture with direct restorations. Coronal fiber-reinforced cusp-coverage direct restoration may be a conservative option for restoring structurally compromised endodontically treated premolars.</p>