In this paper we introduce a new class of diffeomorphic smoothers based on general spline smoothing techniques and on the use of some tools that have been recently developed in the context of image warping to compute smooth diffeomorphisms. This diffeomorphic spline is defined as the solution of an ordinary differential equation governed by an appropriate time-dependent vector field. This solution has a closed form expression which can be computed using classical unconstrained spline smoothing techniques. This method does not require the use of quadratic or linear programming under inequality constraints and has therefore a low computational cost. In a one dimensional setting incorporating diffeomorphic constraints is equivalent to impose monotonicity. Thus, as an illustration, it is shown that such a monotone spline can be used to monotonize any unconstrained estimator of a regression function, and that this monotone smoother inherits the convergence properties of the unconstrained estimator. Some numerical experiments are proposed to illustrate its finite sample performances, and to compare them with another monotone estimator. We also provide a two-dimensional application on the computation of diffeomorphisms for landmark and image matching.