Background The aim of this study was to assess the clinical impact of non-surgical root canal treatments (NSRCT) performed with different treatment protocols on the probability of tooth survival without untoward events and to identify predictors influencing the outcome. Methods During the period from July 1999 to October 2016, 5,858 patients were identified in which 9,967 NSRCTs were performed. The treatments were followed up and divided into three groups. In Group 1 root canal treatment was performed with hand instruments, in Group 2 with multiple file rotary instruments and passive ultrasonic irrigation (PUI), and Group 3 was treated with Reciproc instruments and PUI. Untoward events were defined as orthograde retreatment, apicoectomy or extraction of the tooth after initial treatment. Weibull regression was used to analyse the data. Results A total of 9,938 cases could be included into the analyses. The results showed 5-years predicted survival rates without untoward events of 73.9% (95% CI [71.7%–76.1%]), 75.1% (95% CI [71.7%–78.0%]) and 78.4% (95% CI [75.1%–81.4%]) for study group 1 (N = 5,580), 2 (N = 1,700) and 3 (N = 2,658), respectively. The differences between Group 1 and 3 were statistically significant (p < 0.006). Higher age of the patient (per year increase) and number of earlier NSRCTs (per unit increase) reduce the survival without untoward events statistically significant (both p < 0.02), while treatment of premolars had a statistically significant lower hazard ratio [0.89 (95% CI [0.79–0.99]; p = 0.030)] compared to treatment of molars and anterior teeth. A higher number of supportive periodontal treatments (per unit increase) improved tooth survival without untoward events highly significant (p < 0.0001). Discussion More recent endodontic treatment protocols involving reciprocating instruments and PUI appear to be associated with higher tooth survival rates without untoward events compared to hand instruments.