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PURPOSE To assess the influence of several factors on the survival of tooth-supported fixed partial dentures (FPDs) with vital and non-vital abutments. MATERIALS AND METHODS The present retrospective cohort study was based on the records of patients treated with 3-to-7-unit tooth-supported FPDs with a minimum follow-up time of 6 months after prosthesis delivery. Cumulative survival rate (CSR) was calculated over the maximum follow-up period. Cox regression models were used to evaluate the association between the clinical covariates and prosthesis failure. RESULTS A total of 331 FPDs in 229 patients were included. The CSRs were 90.1% and 77.6% after 5 and 10 years and 67.9% and 52.1% after 15 and 20 years, respectively. Tooth-supported FPD failure was more prevalent within the first years of prosthesis delivery. Loss of one or more abutment teeth and loss of prosthesis retention were the main reasons for failure. Smoking and type of prosthesis material significantly influenced the survival of FPDs. Abutment vitality, position of the non-vital abutment, or prosthesis length did not show any significant influence on the occurrence of prosthesis failure. CONCLUSION Smoking and the type of prosthesis material are suggested to contribute to an increased rate of FPD failure irrespective of abutment vitality.