Purpose: To ascertain whether in the presence of a previously endodontically treated tooth with a periapical pathology and/or symptoms and an uncertain prognosis, it is better to endodontically retreat it or to replace the tooth with a single implant-supported crown., Materials and Methods: Forty patients requiring the treatment of a previously endodontically treated tooth, with a periapical pathology and/or symptoms of endodontic origin and an uncertain prognosis, as judged by the recruiting investigators, were randomly allocated to endodontic retreatment (endo group; 20 patients) or tooth extraction and replacement with an implant-supported crown (implant group; 20 patients) according to a parallel group design at two different centres. Patients were followed to 1 year after completion of the treatment. Outcome measures were: failure of the procedure, complications, marginal bone level changes at both teeth and implants, endodontic radiographic success (teeth only), number of patients' visits and days to complete the treatment, patients' chair time, costs, aesthetics assessed using the pink esthetic score (PES) for the soft tissues and the white esthetic score (WES) for the tooth/crown recorded by independent assessors., Results: No patient dropped out and no complications occurred during the entire follow-up; however, one endodontically retreated tooth (5%) and one implant (5%) fractured, the difference for treatment failures being not statistically significant (difference in proportions = 0; 95% CI -0.14 to 0.14; P Fisher's exact test) = 1.000). The mean marginal bone levels at endo retreatment/implant insertion were 2.34 ± 0.88 mm for the endo and 0.23 ± 0.35 mm for the implant group, which was statistically significantly different (mean difference = 2.11 mm; 95% CI: 1.68 to 2.55; P (t-test) < 0.001). One year after completion of the treatment, teeth lost on average 0.32 ± 0.53 mm and implants 0.48 ± 0.72, the difference not being statistically significant (mean difference = -0.16 mm; 95% CI: -0.58 to 0.27; P (t-test) = 0.457). One year after completion of the endodontic retreatment, of the 13 teeth that originally had a periapical radiolucency, one was lost, six showed complete healing; four a radiographic improvement; and two showed no changes/worsening. Two of the teeth originally without a lesion developed a lesion. There were no statistically significant differences for the number of patients' visits (endo = 5.2 ± 1.8; implant = 5.5 ± 1.1; mean difference = -0.03 95% CI: -1.24 to 0.64; P (t-test) = 0.522). It took significantly more days to complete the implant rehabilitation (endo = 48.9 ± 19.5; implant = 158.5 ± 67.2; mean difference = -109.60; 95% CI: -141.26 to -77.94; P (t-test) < 0.001), but less patients' chair time (endo = 405.5 ± 230.3 min; implant = 260.0 ± 154.6 min; mean difference = 45.50; 95% CI: 19.35 to 271.65; P (t-test) = 0.025). Implant treatment was significantly more expensive (endo = 1195 ± 503.7 €; implant = 1907.5 ± 232.4 €; mean difference = -712.50; 95% CI: -963.59 to -461.41; P (t-test) < 0.001). One year after treatment completion, the mean PES was 10.92 ± 1.93 and 7.07 ± 2.87 and the mean WES was 7.67 ± 1.83 and 7.60 ± 2.32 in the endo group and implant group, respectively. Soft tissues aesthetics (PES) was significantly better at endodontically retreated teeth (mean difference 3.85; 95% CI 1.94 to 5.76; P (t-test) < 0.001) whereas no significant differences were observed for tooth aesthetics (WES) (mean difference 0.07; 95% CI -1.62 to 1.76; P (t-test) = 0.936) between treatments., Conclusions: The preliminary results suggest that both endodontic retreatment and replacement of previously endodontically treated teeth with persisting pathology and a dubious endodontic prognosis provided similar short-term success rates. Aesthetics of the soft tissues and time needed to complete treatment were in favour of endodontic retreatment, whereas implant rehabilitation required half of the chair time than endodontic retreatment, but was significantly more expensive. Although much larger patient populations and longer follow-ups are needed to fully answer this question, in this scenario the less invasive endodontic retreatment could be the first therapeutic option to be considered., Competing Interests: Mozo-Grau/Ticare (Valladolid, Spain), the manufacturer of the implants used in this investigation, donated the implants and partially supported this trial. However, data belonged to the authors and by no means did the sponsor interfere with the conduct of the trial or the publication of its results.