Objective-To evaluate the effects of tylosin on C-reactive protein concentration, carriage of Salmonella enterica, and antimicrobial resistance genes in commercial pigs. Animals-120 pigs on 2 commercial farms. Procedures-A cohort of sixty 10-week-old pigs in 4 pens/farm (15 pigs/pen) was randomly selected. Equal numbers of pigs were given feed containing tylosin (40 μg/g of feed) for 0, 6, or 12 weeks. C-reactive protein concentrations were measured, microbial culture for S enterica in feces was performed, and antimicrobial resistance genes in feces were quantified. Results-No significant associations were detected between C-reactive protein concentration or S enterica status and tylosin treatment. During the 12 weeks of tylosin administration, increased levels of 6 antimicrobial resistance genes did not occur. Conclusions and Clinical Relevance-Treatment of pigs with tylosin did not affect C-reactive protein concentration or reduce carriage or load of S enterica. There was no evidence that pigs receiving tylosin had increased carriage of the 6 antimicrobial resistance genes measured. Impact for Human Medicine-S enterica is a public health concern. Use of the antimicrobial growth promoter tylosin did not pose a public health risk by means of increased carriage of S enterica.