Malpositioned and broken implants are usually fully osseointegrated; hence, their removal, especially from the lower arch, can be very challenging. Implant removal techniques include reverse torque and trephination. Trephination is an invasive technique that can jeopardize vital structures, cause mandibular fatigue fractures, or lead to osteomyelitis. In this study, we aimed to assess the relationship between trephination depth and implant stability by recording implant stability quotient (ISQ) readings at varying trephination depths in vitro. Materials and methods: Forty-eight implants were inserted into dense synthetic polyurethane foam blocks as artificial bone. Primary implant stability was measured with a Penguin resonance frequency analysis (RFA) device. Implants of two designs with a diameter of 3.75 mm and a length of 13 or 8 mm were inserted. Twenty-four internal hexagon (IH) (Seven®) and twenty-four conical connection (CC) implants (C1®; MIS® Implants, Ltd., Misgav, Israel) were used. The primary implant stability was measured with the RFA device. Trephination was performed, and implant stability was recorded at depths of 0, 3, and 6 mm for the 8 mm implants and 0, 3, 6, 8, 10, and 11.5 mm for the 13 mm implants. Results: Linear regression revealed a significant relation between the trephination depth and the ISQ (F (1, 213) = 1113.192, p < 0.001, adjusted r2 = 0.839). The trephination depth significantly predicted the ISQ (β = −5.337, p < 0.001), and the ISQ decreased by −5.33 as the trephination depth increased by 1 mm. Conclusion: Implant stability reduction as measured using an RFA device during trephination may be a valuable guide to achieving safe reverse torque for implant removal. Further studies are needed to evaluate these data in clinical settings.