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Aim: To assess the 18-month success rate of root canal treatment with two integrated shaping and filling systems on upper central incisors with chronic periapical pathosis. Methodology: Sixty patients with an upper central incisors with a chronic periapical lesion smaller than 5 mm in diameter were randomly allocated to two treatment groups, which only differed in terms of canal shaping and filling protocol: G1 (n = 30), Revo-S/One Step Obturator; G2 (n = 30) GTX/GTX Obturator. The patients underwent clinical assessment at baseline and after 6, 12 and 18 months. Radiographic healing was scored according to a previously described scale by two independent examiners, who analysed the periapical radiographs taken at the recall visits. Intra- and inter-observer reliability was tested with Kappa statistics. The significance of the differences between the two groups and among time points with regard to clinical and radiographic data was evaluated with non-parametric tests (p < 0.05). Results: All enrolled patients were available for re-evaluation. At the final recall, the cases were scored as total healing, partial healing and failure with the following frequencies: 93.3%, 3.3% and 3.3% of cases in G1 and in 93.3%, 0% and 6.7% of cases in G2. Radiographic healing scores were similar in the two groups irrespective of the experimental time point. The prevalence of symptoms was scarce (0–10%), stable over time and similar in the two groups. Conclusions: The clinical performance of two considered integrated systems for the endodontic treatment of upper central incisors with periapical lesion was comparable and allowed for high success rates after 18 months.