Few studies focus upon patient-reported outcomes in endodontics. To determine whether full pulpotomy offers a less painful, improved health-related quality of life (HRQoL) compared with root canal treatment (RCT) in cases of irreversible pulpitis (IP) in the 7 days after the treatment. One hundred sixty-eight participants presenting with symptoms of IP were randomized to either pulpotomy (n = 86) or RCT (n = 82). Two participants were excluded, 61 participants underwent full pulpotomy with Biodentine (35.7%), 80 had RCT (46.8%), and 25 were randomized to have pulpotomy which progressed to RCT (PRCT) due to uncontrollable bleeding (14.6%). Clinical and radiographic assessments, using CBCT and periapical radiographs, were carried out preoperatively, for the evaluation of the results only CBCT images were used. Pain (VAS) and HRQoL (EQ 5D) assessments were carried out at baseline and Days 1, 3, 5 and 7 post-baseline. Analysis included descriptive and continuous variables, chi-squared, Fisher's exact, and two-sample t-tests. In pulpotomy and RCT groups, VAS pain decreased significantly over the first week (p < .001). The magnitude of reduction was similar in RCT and pulpotomy (p = .804), RCT and PRCT (p = .179), pulpotomy vs. PRCT (p = .144) and in the comparison of combined RCT /PRCT groups (ORCT) with Pulpotomy (0.729). However, the overall level of VAS pain was significantly higher in the PRCT group than in the Pulpotomy (p = .045) and RCT group (p = .049). Using CBCT, significantly more radiolucencies were found in the PRCT group than in the pulpotomy group and overall teeth presenting with CBCT radiolucencies had significantly higher pain scores (p = .015), particularly at Days 1, 3 and 5. There were significant differences in many OHRQoL domains (Questions 1, 6, 11 and 12) between RCT and PRCT groups with higher frequencies of the impact of oral health problems at Day 0 and Day 7 in the PRCT group. In the treatment of IP, pulpotomy is as effective as RCT in reducing post-operative pain, and improving QoL and HRQoL, teeth displaying uncontrollable bleeding and periapical radiolucencies detected using CBCT are associated with more intense postoperative pain and lower QoL.