Purpose: The aim of this prospective clinical study was to evaluate the survival up to 5 years of Morse cone-connection implants with platform switch considering the influence of biologically relevant, anatomical, and stress-related variables. STROBE guidelines were followed. Materials and Methods: Seven hundred forty-eight implants were inserted in 350 patients. Follow-up visits were scheduled at the time of stagetwo surgery (2 months later) and at 6, 12, 24, 36, and 60 months. All implants were initially loaded with a cemented provisional acrylic restoration. The definitive metal-ceramic restorations were cemented at the 6-month follow-up. Implant cumulative survival rates (CSRs) were calculated using life table actuarial method. Survival data were also analyzed by the log-rank test and Cox regression. The statistical analysis was conducted at the patient level. P ≤ .05 was considered as an indicator of statistical significance. Results: During the follow-up (mean: 40 months; SD: 20.27), 28 patients were considered failed (8%). The CSR and its standard error (SE) was 92% ± 2.17%. Patients with implant-supported single crowns had a CSR of 90%, whereas those with implant-supported fixed dental prostheses had a CSR of 93%. The implant diameter (P = .0399) and implant length (P = .0441) were statistically significant. The probability of failure was almost 75% lower for patients with wide rather than standard implants, 91% lower for patients with long implants, and 69% lower for patients with standard implants compared with short implants. Conclusion: The use of Morse cone-connection implants with platform switch is a safe and reliable treatment method. Stress-related variables influence the risk of failure confirming the importance of biomechanical factors in the longevity of osseointegrated implants; thus, the clinician may obtain better results if attention is paid to these factors. Schlagwörter: cumulative survival rate, dental implant platform switching, dental implants, implant-supported dental prosthesis, Morse-taper dental implant-abutment connection, prospective study