The conventional metal–ceramic is still considered the gold standard in fixed prosthetics especially in terms of longevity. Among alternative materials used, Monolithic Zirconia has shown the capability to reconcile excellent biomechanical properties with acceptable aesthetic performance and to overcome several inconveniences related to veneer restorations. This study aims to clinically evaluate Monolithic Zirconia prosthetic crowns on natural abutments in the posterior sectors, performed by final-year dental medicine students (undoubtedly with less experience in the management of such material) by the standardized California Dental Association score system evaluation, to better understand the viability of Monolithic Zirconia. This prospective study was carried out at the Dental School of the University of Bari “Aldo Moro”, Italy. Prosthetic rehabilitation included single crowns or a short pontic prosthesis with maximum one intermediate. Final-year dental students performed tooth reduction under the supervision of three expert tutors. The California Dental Association systematics (based on color, surface, anatomical shape, and marginal integrity) were adopted to evaluate the prosthetic maintenance status over time. Annual follow-up visits were re-evaluated by the same parameters each year. Univariate logistic regression analysis was performed to evaluate outcomes and the Kaplan–Meier plot to report survival. The sample consists of 40 crowns performed on 31 patients, 15 males (48.4%) and 16 females (51.6%) with an average age of 59.3 years. The clinical cases subjected to experimental study were found to be “Excellent” (1a/2a/3a/4a) in 34 cases (85%), “Acceptable” in 4 cases (10%), and “To be re-done” in 2 cases (failures) (5%). Our conclusive data support the predictability of Monolithic Zirconia restorations on natural posterior abutments at a long-term follow-up of five years, even when performed by less-experienced clinicians.