Purpose: This in vitro study evaluated the effectiveness of a sealing agent on vertical misfit of the implant-abutment interface in an external hexagon implant system before and after mechanical cyclic loading. Effects on preload maintenance of retaining screws after mechanical cycling were also assessed. Materials and Methods: External hexagon implant systems were divided into two groups (n = 12) according to the presence of an anaerobic sealing gel (control group-no sealing gel; experimental group-sealing gel applied). A prefabricated UCLA abutment was attached to the external hexagon implant with a digital torque wrench in accordance with the recommendations of the manufacturer. Specimens were tested through mechanical cyclic loading (1 × 10⁶ cycles, 2 Hz, and 130 N). Vertical misfit of the implant-abutment interface was analyzed using a stereomicroscope, and reverse torque values were obtained using a digital wrench. Misfit and reverse torque data were measured and analyzed via analysis of variance (ANOVA) and the Tukey least significant difference test (α = .05). Results: The sealing gel promoted lower vertical misfit values in the test group after mechanical cycling compared with before cycling (P = .009). The control group showed lower reverse torque values for retaining screws compared with the initial torque after mechanical cyclic loading (P .0001). However, sealing gel application promoted higher reverse torque values in the test group postcycling (P = .0003). Conclusion: Anaerobic sealing agent application improved vertical misfit of the implant-abutment interface and preload maintenance of screw-retained implant-supported prostheses post-mechanical cycling. Keywords: abutment, implant-supported prosthesis, preload, screw