The objective of this work was to evaluate (1) the short-term evolution of pain and (2) the treatment success of full pulpotomy as permanent treatment of irreversible pulpitis in mature molars. The study consisted of a non-randomized comparison between a test group (n = 44)—full pulpotomy performed by non-specialist junior practitioners, and a control group (n = 40)—root canal treatments performed by specialized endodontists. Short-term pain score (Heft–Parker scale) was recorded pre-operatively, then at 24 hours and 7 days post-operatively. Three outcomes were considered for treatment success: radiographic, clinical and global success. For short-term evolution of pain, a non-parametric Wilcoxon test was performed (significance level = 0.05). For treatment success, a Pearson Chi square or Fisher test were performed (significance level = 0.017–Bonferroni correction). There was no significant difference between test and control groups neither regarding short term evolution of pain at each time point, nor regarding clinical (80% and 90%, respectively) or global success (77% and 67%, respectively). However, a significant difference in radiographic success was observed (94% and 69%, respectively). The present work adds to the existing literature to support that pulpotomy as permanent treatment could be considered as an acceptable and conservative treatment option, potentially applied by a larger population of dentists.