Land application of manure from tylosin-treated swine introduces tylosin, tylosin-resistant enterococci, and erythromycin resistant rRNA methylase (erm) genes, which confer resistance to tylosin. This study documents the persistence and transport of tylosin-resistant enterococci,erm genes, and tylosin in tile-drained chisel plow and no-till agricultural fields treated with liquid swine manure in alternating years. Between 70 and 100% of the enterococci in manure were resistant to tylosin and ermB concentrations exceeded 10⁸ copies g⁻¹ manure, while the mean ermF concentrations exceeded 10⁷ copies g⁻¹ manure (ermT was not detected). The mean concentration of tylosin was 73 ng g⁻¹ manure. Soil collected from the manure injection band closely following application contained >10⁹ copies g⁻¹ soil of both ermB and ermF in 2010 and >10⁸ copies g⁻¹ soil after the 2011 application compared to 3 × 10³ to 3 × 10⁵copies g⁻¹ soil in the no-manure control plots. Gene abundances declined over the subsequent 2-yr period to levels similar to those in the no-manure controls. Concentrations of enterococci in tile water were low, while tylosin-resistant enterococci were rarely detected. In approximately 75% of tile water samples, ermB was detected, and ermF was detected in 30% of tile water samples, but levels of these genes were not elevated due to manure application, and no difference was found between tillage practices. These results show that tylosin usage increased the short-term occurrence of tylosin-resistant enterococci, erm genes, and tylosin in soils but had minimal effect on tile drainage water quality in years of average to below average precipitation.