Objective The objectives of this study were to evaluate the effect of a CAD/CAM nickel‐titanium retainer on the stability of mandibular anterior teeth and periodontal health and to compare it with other retainers. Setting/Sample Population Sixty participants from both genders who had irregularities prior to orthodontic therapy and who had been treated with full‐fixed appliance mechanotherapy were included in the study and randomly allocated into four groups: CAD/CAM NiTi, multi‐stranded stainless steel, single‐stranded nickel‐free titanium and vacuum‐formed removable retainer groups. The mean age of the participants at the end of the treatment was approximately 20 years. Materials and Methods Digital impressions were taken for all participants at three different times: immediately (T0), three months (T1) and six months (T2) after treatment. Irregularity index, inter‐canine and inter‐molar width, and arch length were recorded using software. Additionally, a full periodontal assessment was carried out at T2. Results During the follow‐ups, all groups showed some relapse in the lower anterior teeth. No statistical significance was found intergroup in terms of all measured values. Within the multi‐stranded group, inter‐canine width had decreased by 0.10 mm with a statistical significance (P = .048). An additional statistical significance with P = .045 was found within the single‐stranded group regarding the increased arch length. The periodontal assessment results of the mandibular anterior teeth between groups did not show clinically significant differences. Conclusion No statistical significance was found between the CAD/CAM retainer and other retainers regarding the clinical failure rate. Less plaque accumulation and gingival inflammation were observed in the CAD/CAM NiTi retainer group.