It is proved a characterization theorem for semi-classical orthogonal polynomials on non-uniform lattices that states the equivalence between the Pearson equation for the weight and some systems involving the orthogonal polynomials as well as the functions of the second kind. As a consequence, it is deduced the analogue of the so-called compatibility conditions in the ladder operator scheme. The classical orthogonal polynomials on non-uniform lattices are then recovered under such compatibility conditions, through a closed formula for the recurrence relation coefficients.