Salmonella typhi, causative agent of typhoid fever, a predominantly human communicable disease, is endemic in Africa and Asia. S. typhi is of clinical importance partly due to its mode of infection and partly due to the fact that human activities such as poor hygienic conditions are essential in the transmission and perpetuation of the pathogen. More so antibiotic resistant strains of S. typhi have emerged, increasing cost of treatment, morbidity and mortality. Meanwhile, S. typhi isolation and sensitivity testing to antibiotics are rarely practiced in the hospitals in and around Kumasi. This study sought to determine the extent of antibiotic susceptibility of S. typhi isolated from patients in Kumasi south, North Suntreso and Tafo hospitals in the Ashanti region of Ghana. The isolates were identified using morphological and biochemical means. The isolates were then tested for their sensitivity to some reference antibiotics using the Kirby-Bauer disc diffusion method. One hundred and twenty-eight (128) S. typhi were isolated from 900 clinical samples. A total of 52.3% of the S. typhi isolates exhibited resistance to ampicillin whereas 32.8, 25.0, 17.2 and 14.9% of the isolates were resistant to co-trimoxazole, chloramphenicol, ciprofloxacin and ceftriaxone respectively. About 19.5% of the S. typhi isolates were multidrug resistant. The S. typhi isolates were most sensitive to ciprofloxacin and ceftriaxone whilst majority of the S. typhi tested were resistant to ampicillin. Ampicillin is therefore no longer suitable for the treatment of S. typhi infections in these hospitals.