Milk thistle can be an annual, rarely a biennial medicinal plant. Polyfactorial field experiment was established during the vegetation period of the years 2012-2015. Three evaluated factors were as follows: crop residues -intercrop -fertilization. Milk thistle was integrated to four crop rotation design with following order of crops: 1. common pea 2. winter wheat 3. milk thistle 4. maize. Milk thistle was subjected to the experimental treatments as follows: 1. K -straw of forecrop removed from the field, R -straw incorporated into soil, 2. M -white mustard as a freezing-out intercrop, B -no intercrop, 3. O -no fertilization, F -with fertilization, 4. experimental year (2012, 2013, 2014, 2015). The recalculated yield of Silybi mariani fructus ranged in the amount from 297 kg*ha -1 (RMO treatment -with crop residues, with intercrop and without the use of fertilizers, year 2015) to 745 kg*ha -1 (KMF treatment -without crop residues, with intercrop and the use of fertilizers, year 2013). Statistical testing of individual factors found highly significant effect of year and highly significant effect of fertilization, and statistically inconclusive effect of sowing intercrop and ploughing crop residues. In the experiment was found a statistically significant difference between yield on the treatments without fertilization and the use of mineral fertilizers.