The main purpose of the article is to assess the economic efficiency of wheat protection in conditions of the occurrence of weed resistance to herbicides in a selected large-scale farm (case study). In modern agriculture, especially in large-scale farms using monoculture, zero tillage and intensive chemical protection, the emerging phenomenon of weed resistance to herbicides is a cause of ecological and economic losses. In Poland, as well as the world, the problem of weed resistance is mainly noted in the case of wheat cultivation, which is ranked first in terms of sown area. Therefore, more and more often attempts are being made to answer the question, what is the profitability of performed weed control operations with the simultaneous occurrence of herbicide resistance. Empirical research was conducted on the basis of data recorded in the book of profits and losses recorded by the farm owner in 2014-2018. The collected data was developed using economic analysis and statistical methods. It was found that, in the examined period, due to the growing problem of the presence of resistant weeds, the use of products to control them increased and the costs of protecting wheat cultivation also increased. The low effectiveness of chemical weed control treatments resulted in a change in the structure of crops in the researched farm in the last year of the study.