Salmonella enterica are among the foodborne pathogens of importance due to their involvement in a number of foodborne outbreaks, illnesses and occasionally death. This study was carried out in the Tamale metropolis of Ghana to investigate the prevalence and antibiotic resistance of Salmonella enterica in cow milk, cow milk products and hands of cow milk sellers. The conventional method and the disc diffusion method were used for the isolation and antibiotic resistance of Salmonella enterica, respectively. The overall prevalence of Salmonella enterica was 7.3% (22/300). Salmonella enterica were detected in 24.0% (12/50) of raw 'wagashie', 8.0% (4/50) of fried 'wagashie', 6.0% (3/50) of cow milk, 4.0% (2/50) of left hand swab of milk sellers, and 2.0% (1/50) of right hand swab of milk sellers. Salmonella enterica was not isolated from 'brukina'. The prevalence of Salmonella enterica did not differ (P = 0.193) among fried 'wagashie', cow milk, hand swab of milk sellers and 'brukina' samples. However, the prevalence of Salmonella enterica in raw 'wagashie' was significantly higher (P = 0.000) than the other samples examined. Resistant to erythromycin (86.0%) was most frequently detected. The Salmonella enterica isolates were highly susceptible to ciprofloxacin (100.0%), chloramphenicol (91.0%), ceftriaxone (91.0%), sulphamethoxazole/trimethoprim (91.0%), tetracycline (86.0%) and ampicillin (86.0%). Of the 22 Salmonella enterica isolates, 14 were resistant to only one antibiotic, 4 were resistant to two antibiotics and 2 were resistant to three antibiotics. Two Salmonella enterica isolates were resistant to none of the antibiotics. This study revealed that some milk products and other samples were contaminated with Salmonella enterica. The isolated Salmonella enterica were susceptible to most of the antibiotics examined but were highly resistant to erythromycin.