A new approach for sites prioritization and designing measures on land drainage was developed and tested on the 96.5 km2 Žejbro catchment (Czech Republic). The aim was to design an effective, mutually interconnected system of measures, on tiles, manholes, outlets as well as on ditches (s.c. main drainage facilities, MDF) that will increase water retention and storage in intensively farmed and tile-drained catchments and will reduce water pollution from subsurface non-point sources (drainage runoff). This approach consists of (I) selecting suitable sites using the Catchment Measures Need Index (CAMNI) method; (II) obtaining information on land drainage in the area of interest; (III) conducting a field survey and water quality monitoring; (IV) designing appropriate systems of measures; and (V) analysing the estimated costs of the proposed measures. Measures were proposed for fourteen sub-catchments that were selected based on the results of a CAMNI analysis and whether an MDF or a heavily modified stream is present. A total of 44 point measures, 62 areal measures, and 99 line measures were proposed. Implementation of these measures would reduce the load of N-NO3, a major pollutant from drainage runoff, by 44 tons per year (48%). From the financial point of view, these measures are not self-financing and the benefits do not cover the expected costs of their implementation and maintenance. However, these measures have a profound ecological and societal benefits which, when taken into account, make these measures suitable for implementation when (co-)financed from public budgets. Putting the presented approach into practice, for example, in the framework of complex land consolidations or by watershed management authorities, could significantly improve the condition and water regime of intensively drained agricultural landscapes.