Abstract Objectives: In this paper, we propose a novel registration technique, which combines the concepts of landmark and automatic, non-rigid intensity based approaches. A general framework which might be used for many different registration problems is presented. The novel approach enables the incoorporation of different distance measures as well as different smoothers. Methods: The proposed scheme does minimize a regularized distance measure subject to some interpolation constraints. The desired deformation is computed iteratively using an Euler-scheme for the first variation of the chosen objective functional. Results: A fast and robust numerical scheme for the computation of the wanted minimizer is developped, implemented, and applied to various registration tasks. This includes the registration of pre- and post intervention images of human eye. Conclusions: A novel framework for parameter-free, non-rigid registration scheme which allows for the additional incorporation of user defined landmarks is proposed. It enhances the reliability of conventional approaches considerably and thereby their acceptability by practitioners in a clinical environment.