The antibiotics Exceed and Excenel are two formulations of the cephalosporin drug ceftiofur that are commonly used to treat finishing pigs in the US. Our object was to understand the relationship between the use of ceftiofur and the spread of important cephalosporin resistance genes in swine finishing barns. To accomplish this we collected approximately 30 fecal samples from each of 50 finishing barns located in 5 US states. We tested the samples for the presence of Escherchia coli or Salmonella that were resistant to ceftiofur and other important antibiotics. Any isolates resistant to ceftiofur were then tested for specific genes that provide resistance to important cephalosporins known as blaCTX-M and blaCMY. Of the 1495 total fecal samples that were tested, 109 (7.3%) from 25 barns were positive for Salmonella, but only 2 of those carried the blaCMY gene and were resistant to ceftiofur. A total of 1174 (78.5%) of the fecal samples contained E. coli with the blaCMY gene, but only 24 (1.6%) contained E. coli or other bacteria with the blaCTX-M gene. Pigs were commonly treated with ceftiofur as pigs in 41 (82%) of the barns had been exposed to ceftiofur prior to finishing in either farrowing or nursery barns. In addition, individual sick pigs in 24 (48%) finishing barns received ceftiofur for treatment. However, this reported ceftiofur use was not associated with the presence of E. coli carrying blaCTX-M or blaCMY. This result suggests that the spread of resistant bacteria in swine finishing barns cannot be fully explained by simply measuring antibiotic use. Attempts to reduce resistance will likely require that complex relationships of factors be identified that promote the spread of resistant organisms and resistance genes.