Background: Recently several calcium silicate flowable sealers have been introduced as endodontic materials for the root canal. This clinical study tested the use of a new premixed calcium silicate bioceramic sealer in association with the Thermafil warm carrier-based technique (TF). Epoxy-resin-based sealer with the warm carrier-based technique was the control group. Methodology: Healthy consecutive patients (n = 85) requiring 94 root canal treatments were enrolled in this study and assigned to one filling group (Ceraseal-TF n = 47, AH Plus-TF n = 47) in accordance with operator training and best clinical practice. Periapical X-rays were taken preoperatively, after root canal filling and after 6, 12 and 24 months. Two evaluators blindly assessed the periapical index (PAI) and sealer extrusion in the groups (k = 0.90). Healing rate and survival rate were also evaluated. Chi-square tests was used to analyze significant differences between the groups. Multilevel analysis was performed to evaluate the factors associated with healing status. Results: A total of 89 root canal treatments in 82 patients were analyzed at the end-line (24 months). The total drop-out was 3.6% (3 patients; 5 teeth). A total of 91.1% of healed teeth (PAI 1-2) was observed in Ceraseal-TF, with 88.6% in AH Plus-TF. No significant difference was observed on healing outcome and survival among the two filling groups (p > 0.05). Apical extrusion of the sealers occurred in 17 cases (19.0%). Of these, 6 occurred in Ceraseal-TF (13.3%) and 11 in AH Plus-TF (25.0%). Three Ceraseal extrusions were radiographically undetectable after 24 months. All the AH Plus extrusions did not change during the evaluation time. Conclusions: The combined use of the carrier-based technique and premixed CaSi-based bioceramic sealer showed clinical results comparable with carrier-based technique and epoxy-resin-based sealer. The radiographical disappearance of apically extruded Ceraseal is a possible event in the first 24 months.