This work aims to test accuracy and comparability of 3D models of human skeletal fibulae generated by clinical CT and laser scanner virtual acquisitions. Mesh topology, segmentation and smoothing protocols were tested to assess variation among meshes generated with different scanning methods and procedures, and to evaluate meshes‐interchangeability in 3D geometric morphometric analysis. A sample of 13 left human fibulae were scanned separately with Revolution Discovery CT dual energy (0.625 mm resolution) and ARTEC Space Spider 3D structured light laser scanner (0.1 mm resolution). Different segmentation methods, including half‐maximum height (HMH) and MIA‐clustering protocols, were compared to their high‐resolution standard generated with laser‐scanner by calculating topological surface deviations. Different smoothing algorithms were also evaluated, such as Laplacian and Taubin smoothing. A total of 142 semilandmarks were used to capture the shape of both proximal and distal fibular epiphyses. After Generalized Procrustes superimposition, the Procrustes coordinates of the proximal and distal fibular epiphyses were used separately to assess variation due to scanning methods and the operator error. Smoothing algorithms at low iteration do not provide significant variation among reconstructions, but segmentation protocol may influence final mesh quality (0.09–0.24 mm). Mean deviation among CT‐generated meshes that were segmented with MIA‐clustering protocol, and laser scanner‐generated ones, is optimal (0.42 mm, ranging 0.35–0.56 mm). Principal component analysis reveals that homologous samples scanned with the two methods cluster together for both the proximal and distal fibular epiphyses. Similarly, Procrustes ANOVA reveals no shape differences between scanning methods and replicates, and only 1.38–1.43% of shape variation is due to scanning device. Topological similarities support the comparability of CT‐ and laser scanner‐generated meshes and validate its simultaneous use in shape analysis with potential clinical relevance. We precautionarily suggest that dedicated trials should be performed in each study when merging different data sources prior to analyses.