The purpose of this randomized controlled clinical trial was to assess the short-term clinical effectiveness of sealer-based root canal obturation using calcium-silicate-based sealer (CSBS) and epoxy-resin-based sealer (ERBS). A total of eighty patients (eighty teeth) were enrolled and seventy-two patients (seventy-two teeth) were randomly assigned into four different sealer groups: AH Plus (AH, Dentsply Sirona), ADseal (AD, Meta Biomed), CeraSeal (CS, Meta Biomed), or EndoSeal TCS (ES, Maruchi). At the first visit, root canal treatment was performed using ProTaper. Next, the NiTi file system and passive ultrasonic irritation was applied with 2.5% NaOCl. At the second visit, the teeth were obturated with a sealer-based obturation technique using the assigned sealer. The quality of filling obturation was evaluated with postoperative radiographs in terms of the presence of voids and sealer extrusion. The patients were recalled at 1-week, 1-month, and 3-month intervals, and pain levels were measured using visual analog scales (VAS), and clinical examination performed with percussion and palpation. Radiographs were also taken. The results were statistically compared by using the χ2 test or Fisher exact test. Among the 80 teeth included, 72 teeth received allocated intervention and 71 teeth were included in the analysis (98.6% recall). There was no significant difference among the sealers in void and sealer extrusion (p > 0.05). Postoperative pain was not indicated prominently regardless of the type of sealer. For a 3-month follow-up period, all cases were maintained successfully except for one case from AD. According to the findings, there was no significant difference between CSBS and ERBS in terms of postoperative pain or the healing process, and the variation in filling quality appears to be linked to the properties of each product.