The aim of this pilot study was to evaluate the accuracy of two different methods of navigated retrograde drilling of talar lesions. Artificial osteochondral talar lesions were created in 14 cadaver lower limbs. Two methods of navigated drilling were evaluated by one examiner. Navigated Iso-C^3D was used in seven cadavers and 2D fluoroscopy-based navigation in the remaining seven. Of 14 talar lesions, 12 were successfully targeted by navigated drilling. In both cases of inaccurate targeting the 2D fluoroscopy-based navigation was used, missing lesions by 3 mm and 5 mm, respectively. The mean radiation time was increased using Iso-C^3D navigation (23 s; 22 to 24) compared with 2D fluoroscopy-based navigation (14 s, 11 to 17).