AimThis 60‐month prospective study aimed to evaluate tooth survival and healing rates after root canal treatment in patients taking bisphosphonates (BPs). Secondary outcomes were complications and clinical variables observed during and after treatment.MethodsRoot canal treatment was performed using manual K‐file canal instrumentation and a carrier‐based filling technique with an epoxy resin‐based sealer. Teeth without adequate root/crown integrity were restored by trained operators at the tissue level (TL group) to prevent occlusal/mechanical stress and to enable periapical lesion healing without the risk of root fracture. Other teeth were restored with normal occlusal contacts (OC group). Healthy patients who had undergone one or more root canal treatments of the same type constituted the control group. The relationships of the following variables to survival and health status were examined (chi‐squared test and multivariate analysis, P = 0.05): age, gender, smoking habit, tooth location, treatment type, BPs treatment, BPs exposure, initial periapical index (PAI) and occlusal restoration. Survival curves were constructed using Kaplan–Meier analysis, with extraction serving as the end‐point.ResultsIn total, 65 patients with 109 root canal‐treated teeth who were taking BPs were included. At 60 months, data from 57 patients (52F, 5M; median age 65.7 ± 8.6 years) who had undergone 96 root canal treatments were analysed (drop‐out rate = 16.9%). The survival rate was 85%, and the success rate was 76%. The control group consisted of 46 patients (21F, 25M; median age 60.3 ± 7.2 years) who had undergone 102 root canal treatments. The survival rate was 88%, with 12 teeth lost during follow‐up. The success rate was 73%. In the BP group, 55 teeth were restored normally (OC group) and 41 teeth were restored at the tissue level (TL group). No difference in the success or survival rate was observed between the BP and control groups (P > 0.05). Univariate Kaplan–Meier analysis revealed that only tooth type significantly affected survival status in the BP group. The analysis revealed the clinical relevance of smoking, tooth location and initial PAI on patients’ health status (P < 0.05).ConclusionRoot canal treatments and post‐endodontic restoration with tissue‐level filling procedures represent a safe approach for severely damaged teeth in patients receiving BPs having comparable results to root filled teeth restored with occlusal contacts and to the control group.