Purpose: To measure the microgap between dental implants and custom abutments fabricated using different computer-aided design/computer-aided manufacture (CAD/CAM) methods before and after mechanical cycling. Materials and Methods: CAD software (Dental System, 3Shape) was used to design a custom abutment for a single-unit, screw-retained crown compatible with a 4.1-mm external hexagon dental implant. The resulting stereolithography file was sent for manufacturing using four CAD/CAM methods (n = 40): milling and sintering of zirconium dioxide (ZO group), cobalt-chromium (Co-Cr) sintered via selective laser melting (SLM group), fully sintered machined Co-Cr alloy (MM group), and machined and sintered agglutinated Co-Cr alloy powder (AM group). Prefabricated titanium abutments (TI group) were used as controls. Each abutment was placed on a dental implant measuring 4.1 × 11 mm (SA411, SIN) inserted into an aluminum block. Measurements were taken using scanning electron microscopy (SEM) (×4,000) on four regions of the implant-abutment interface (IAI) and at a relative distance of 90 degrees from each other. The specimens were mechanically aged (1 million cycles, 2 Hz, 100 N, 37°C) and the IAI width was measured again using the same approach. Data were analyzed using two-way analysis of variance, followed by the Tukey test. Results: After mechanical cycling, the best adaptation results were obtained from the TI (2.29 ± 1.13 μm), AM (3.58 ± 1.80 μm), and MM (1.89 ± 0.98 μm) groups. A significantly worse adaptation outcome was observed for the SLM (18.40 ± 20.78 μm) and ZO (10.42 ± 0.80 μm) groups. Mechanical cycling had a marked effect only on the AM specimens, which significantly increased the microgap at the IAI. Conclusion: Custom abutments fabricated using fully sintered machined Co-Cr alloy and machined and sintered agglutinated Co-Cr alloy powder demonstrated the best adaptation results at the IAI, similar to those obtained with commercial prefabricated titanium abutments after mechanical cycling. The adaptation of custom abutments made by means of SLM or milling and sintering of zirconium dioxide were worse both before and after mechanical cycling. Keywords: CAD/CAM, dental implant, external abutment connection, implant-abutment interface, microgap, misfit