Clinical evidence is lacking regarding the influence of the amount of residual coronal dentin and of post placement on the failure risk of endodontically compromised teeth. The aim of this prospective clinical trial was to assess whether these factors significantly affect the two-year survival of restored pulpless premolars. A sample of 210 individuals provided six experimental groups of 40 premolars in need of endodontic treatment. Groups were defined based on the amount of dentin left at the coronal level. Within each group, in half of the teeth selected at random, a fiber post was inserted inside the root canal, whereas in the remaining half of the premolars, no post was placed. All teeth were covered with a crown. The Cox regression analysis revealed that post placement resulted in a significant reduction of failure risk (p < 0.001). Failure risk was increased for teeth under the "no ferrule" (p = 0.001) and "ferrule effect" conditions (p = 0.004).