Ankle arthrodesis is the gold standard for treatment of end-stage arthritis. The goal of ankle arthrodesis is to obtain bony union between the tibia and the talus. Retrograde intramedullary nailing is typically reserved for ankle and subtalar joints arthrodesis. The purpose of this study is to evaluate the effect of two different materials, two locking pin configurations and two nail designs of a retrograde locked intramedullary nail used for ankle arthrodesis. Using the finite element analysis, a numerical study of ankle arthrodesis was developed to evaluate the effect of materials: TI-6Al-4V and stainless steel AISI 316 LVM; two locking pin configurations: five and six pins, on two intramedullary nails: Ø10 × 180 mm and Ø11 × 200 mm. A model of a healthy foot was created from tomographic scans. It was found that the mechanical stimulus required to achieve bone fusion were higher for Ø10 × 180 nails (6.868 ± 0.047) than the Ø11 × 200 nails (5.918 ± 0.047; p < 0.001; mean ± SEM). We also found that six-pin configuration had a higher mechanical stimulus (6.470 ± 0.047) than the five-pin configuration (6.316 ± 0.046; p = 0.020). Similarly, it was higher for titanium (6.802 ± 0.047) than those for stainless steel (5.984 ± 0.046; p < 0.001). Finally, the subtalar zone presented higher values (7.132 ± 0.043) than the tibiotalar zone (5.653 ± 0.050; p < 0.001). The highest mechanical stimulus around the vicinity of tibiotalar and subtalar joint was obtained by Ø10 × 180 nails, made of titanium alloy, with 6P.