This investigation determined the frequency of resistance of 84 isolates of Salmonella comprising 14 serotypes recovered from layer farms in three Caribbean countries (Trinidad and Tobago, Grenada, and St. Lucia) to eight antimicrobial agents, using the disc diffusion method. Resistance among isolates of Salmonella was related to the country of recovery, type of sample, size of layer farms, and isolate serotype. Overall, all (100.0%) of the isolates exhibited resistance to one or more of seven antimicrobial agents tested, and all were susceptible to chloramphenicol. The resistance detected ranged from 11.9% to sulphamethoxazole-trimethoprim (SXT) to 100.0% to erythromycin. The difference was, however, not statistically significant (P = 0.23). Across countries, for types of samples that yielded Salmonella, significant differences in frequency of resistance were detected only to SXT (P = 0.002) in Trinidad and Tobago and to gentamycin (P = 0.027) in St. Lucia. For the three countries, the frequency of resistance to antimicrobial agents was significantly different for ampicillin (P = 0.001) and SXT (P = 0.032). A total of 83 (98.8%) of the 84 isolates exhibited 39 multidrug resistance patterns. Farm size significantly (P = 0.032) affected the frequency of resistance to kanamycin across the countries. Overall, among the 14 serotypes of Salmonella tested, significant (P < 0.05) differences in frequency of resistance were detected to kanamycin, ampicillin, and SXT. Results suggest that the relatively high frequency of resistance to six of the antimicrobial agents (erythromycin, streptomycin, gentamycin, kanamycin, ampicillin, and tetracycline) tested and the multidrug resistance detected may pose prophylactic and therapeutic concerns for chicken layer farms in the three countries studied.