Widespread use of antibiotics in U.S. livestock operations has been identified as a potential contributor to the rising rates of antibiotic-resistant bacterial infections. In response, the U.S. Food and Drug Administration (FDA) issued new rules in January 2017. GFI (Guide for Industry) #213 banned use of antibiotics for growth promotion and required veterinarian permission, via a revised Veterinary Feed Directive (VFD), to deliver antibiotics through feed. Many stakeholders expressed pre-implementation concerns regarding the rules' potential adverse effects on production and profitability. Our study employed qualitative and quantitative methods to investigate how implementation of GFI #213/VFD impacted Ohio cattle operations. We interviewed over fifty cattle farmers and eight large animal veterinarians to document changes in farm antibiotic use, management practices, and profitability. We also examined published government data for possible effects on overall meat production at the state and national levels. We found that the great majority of Ohio farmers reported little difficulty in complying with the VFD with minimal adverse impacts. Farm responses to the feed directive varied with operation size, type (beef or dairy), and whether producers had previously used fed antibiotics. The most commonly reported changes, by both producers and veterinarians, were more veterinary-client interactions, more paperwork/record-keeping, and decreased use of fed antibiotics. All veterinarians, many beef operators, but no dairy operators reported perceiving the VFD as beneficial; however, dairy operations reported less difficulty with compliance due to established working relationships with veterinarians. We found no evidence that the rules impacted the trajectory of state or national livestock output. In conclusion, GFI #213 was reported as not burdensome enough to prevent compliance, but inconvenient enough to incentivize reduced use of fed antibiotics (when previously used) without significant adverse effects, consistent with its goal of promoting judicious use of medically important antibiotics in order to preserve their effectiveness.