The realization of the Hofstadter model in a strongly anisotropic ladder geometry has now become possible in one-dimensional optical lattices with a synthetic dimension. In this work, we show how the Hofstadter Hamiltonian in such ladder configurations hosts a topological phase of matter which is radically different from its two-dimensional counterpart. This topological phase stems directly from the hybrid nature of the ladder geometry, and is protected by a properly defined inversion symmetry. We start our analysis considering the paradigmatic case of a three-leg ladder which supports a topological phase exhibiting the typical features of topological states in one dimension: robust fermionic edge modes, a degenerate entanglement spectrum and a non-zero Zak phase; then, we generalize our findings -addressable in the state-of-the-art cold atom experiments -to ladders with an higher number of legs. The Hofstadter problem [1] describing a particle hopping on a two-dimensional lattice pierced by a magnetic field, is a paradigm of quantum mechanics. Formulated more then forty years ago, it embeds a multitude of seminal notions in modern condensed matter physics [2]: topological bands, edge excitations, fractal properties of the spectrum, just to mention some of them. Despite its apparent simplicity and the enormous body of investigation both theoretical and experimental [3][4][5][6][7], the Hofstadter problem still hides some surprises, as we are going to discuss in the following.The motivation of our work stems from the recent realization [8-10] of the Hofstadter Hamiltonian in optical lattices with a synthetic dimension. The possibility of engineering an additional (synthetic) few sites long dimension [11,12] with non-trivial boundary conditions by using some internal degrees of freedom of the atoms has encouraged the study of the Hofstadter Hamiltonian in a strongly anisotropic geometry [13].(a) Is this a new territory for the Hofstadter problem or are we bound to detect a smooth crossover from a two-to a one-dimensional behavior? A naïve expectation would induce to think that synthetic lattices can simulate a two-dimensional geometry when the transverse dimension is much longer than the correlation length of the system along the transverse dimension itself, and they turn out to be effectively one-dimensional when the number of sites in the transverse direction is small, such as in synthetic ladders. In this work, we show that in the presence of a selected applied magnetic field and for an odd number of legs (L y ), this simple picture fails and the Hofstadter Hamiltonian can host unexpected topological phases for suitable values of the flux piercing the ladder. These phases, addressable in the state-of-the-art cold-atom experiments [8,9], are protected by a hidden inversion symmetry and exhibit the typical features of topological states in one dimension, i.e., exponentially localized degenerate edge states, a non-zero Zak phase [14][15][16], and a degenerate entanglement spectrum [17,18]. Note, however, that they...