The rate of prescription of cephalosporins especially the second and third generation and the spread of resistance among members of Enterobacteriaceae has become a reason for concern. This study was designed to determine the rate of prescription and resistance to the 2nd and 3rd-generation cephalosporins to Enterobacteriaceae in the Ekiti State University Teaching Hospital, Ado Ekiti. A retrospective study of prescription forms and laboratory reports were used in collecting the data. A total of 9,234 prescriptions issue within May 2017 to May 2018 were collected. Five thousand five hundred and twenty one (59.8%) prescriptions sheets contain at least one antibiotic. Three thousand seven hundred and thirteen prescriptions 3,713 (40.2%) did not contain any antibiotics. It was observed that Cephalosporins were the most commonly prescribed, while tetracycline was the least with 1584(28.7%) and 1076(19.5%) respectively. Cefuroxime had the highest rate of prescription with 898(57.9%) while cefpodoxime was the least prescribed with 33(2.1%). Out of the 201 diagnosed infections in patients who used cephalosporins, 83 (41.3%) were caused by members of Enterobacteriaceae. E.coli was the most common cause of infections of all the members of Enterobacteriacea with 32.5%. Of all the members of Enterobacteriaceae, 64.2% were resistant to cephalosporin. E.coli had the highest resistance to cephalosporins while Salmonella sp had the lowest resistance with 34(22.5%) and 13(8.6%) respectively. The data obtained from this study showed that there is a significant difference between the rate of prescription of cephalosporins and other antibiotics. Also there was an excessive prescription of the second and third generation cephalosporins. In conclusion the rate of prescription of cephalosporin should be properly checked and laboratory investigations should be properly conducted before administration.