High-quality, prospective clinical studies are needed to increase evidence for guided endodontics. This study aims to assess the clinical outcome of guided endodontics for treatment of teeth presenting with pulp canal obliteration (PCO) in comparison with freehand treatment. This trial was registered in the ISRCTN.com registry (ISRCTN75277265) and designed as a controlled clinical trial: Single arm trial, prospective, nonrandomized, single-centre study (ethical approval number S64630). Inclusion criteria were; tooth presenting with PCO and symptoms and/or signs of apical periodontitis (AP). An external control group was selected from clinical records of patients presenting the same criteria but treated freehanded. Guided root canal treatments were performed by the same operator on all patients. Freehanded treatments were performed by a specialist in endodontics under microscope with pre-operative CBCT available. Primary outcome for both groups was evaluated as: canal found, canal not found, or perforation. As secondary outcome, the qualitative accuracy of the drill path was assessed as: optimal precision, acceptable precision or technical failure. Patients were followed up yearly. Descriptive statistics on the study patient's demographics and healing outcome were performed and specific statistical analysis was performed on each outcome variable. A total of 133 teeth were included (n = 60 guided, n = 73 freehanded) from 128 patients (n = 59 guided, n = 69 freehanded). The primary outcome for the guided group was: 59 teeth canals found and 1 tooth canal not found. No perforations were recorded. In the freehanded group, the root canal was successfully found in 59 teeth, seven were not found, and seven had a perforation. An analysis of all data showed that guided endodontics presented statistically significant better outcome than freehand treatment (p < .05). Guided endodontics showed a statistically significant better outcome than freehanded treatment resulting in less technical failures. However, it is a complex procedure which should be carried out by an experienced endodontist with the aid of a dental microscope.