Radiostereometric analysis (RSA) is the current gold standard to determine implant migration, but it requires bone markers and special equipment. Therefore, we developed VoluMetric Matching Micromotion Analysis (V3MA), a software program for Computed Tomography-based radiostereometric analysis (CT-RSA). This study aimed to determine the accuracy and precision of V3MA in vitro compared to RSA and provide a clinical proof of concept. The accuracy (RMSE (Root Mean Squared Error)) and precision (SD (standard deviation)) of V3MA were compared to RSA. A tibial component was placed in 21 different positions within a cadaveric bone to assess accuracy. For precision, a total of 20 repeated zero-migration examinations from 4 cadaveric bones with cemented tibial components were performed. In 6 total knee arthroplasty (TKA) patients 1 to 5 year migration was measured with V3MA and RSA. V3MA accuracy ranged between 0.02 and 0.09 mm for translations and was 0.01° for internal–external rotations. For RSA, the accuracy ranged between 0.03 and 0.09 mm for translations and was 0.09° for internal-external rotations. V3MA precision ranged between 0.01 and 0.06 mm for translations and 0.02 to 0.07° for rotations. RSA precision ranged between 0.00 and 0.06 mm for translations and 0.04 to 0.25° for rotations. V3MA was successful in 6 clinical cases and no systematic bias was present. In conclusion, the accuracy and precision of V3MA were similar to RSA. Therefore, V3MA is a promising alternative to RSA in migration measurements of tibial components in TKA.