Pose and twist estimation is a ubiquitous problem in science and engineering: from astro- and aeronautics to biomechanics; from navigation systems to the latest video games. Current technology relies mainly upon accelerometer strapdowns, which call for precise estimation algorithms. Along these lines, the main objective of this dissertation is the development of innovative accelerometer strapdowns suitable for estimating rigid-body pose and twist accurately and reliably. The design philosophy is based on two interdependent concepts: an original concept of biaxial accelerometers, introduced in a previous dissertation and termed Simplicial Biaxial Accelerometers (SBA), and isotropic accelerometer strapdowns. The goal of the former is to sense accelerations along arbitrary directions in a plane. An improved SBA design is proposed and realized by means of MEMS (Microelectromechanical System) fabrication technology. By means of finite element analysis (FEA), the accelerometer sensitivity was found to be highly acceptable. The analysis results show that the SBA is isotropically sensitive to accelerations along arbitrary directions in the plane, while the cross-axis sensitivity is reduced, as desired. Isotropy mainly concerns a novel accelerometer strapdown made of the proposed SBAs. By virtue of its inherent geometric isotropy, the tetrahedral SBA strapdown is selected, but other isotropic polyhedra, such as the other four Platonic solids and Buckyballs, can be equally used. Performance and accuracy of the strapdown in estimating the pose and the twist of a rigid-body moving in space are illustrated with representative simulation examples. Moreover, the isotropic nature of the strapdown enables the decoupling of the point tangential acceleration from its centripetal counterpart in the acceleration field. Consequently, “coupling”—a major hurdle in pose and twist estimation—is avoided, thereby streamlining the estimation process.