In this study, we describe the prevalence of TB and occurrence of multidrug-resistance tuberculosis (MDR-TB) in a major referral hospital belonging to the Ministry of Health in Sharjah, United Arab Emirates (UAE). A retrospective review of the clinical and laboratory records of 1,810 suspected cases of TB was carried out between January 2004 and September 2008. The antimicrobial susceptibility patterns of each Mycobacterium tuberculosis isolate were analyzed. During the study period, 312 M. tuberculosis culture confirmed cases were recorded; 230 were males and 82 were females. The majority of TB cases (36%) were seen among expatriates from South and Southeast Asian countries. Fifty-one active TB cases (16%) were reported in native people (Emaratis) of the country. The peak age group was between 16 and 45 years. Among first-line antituberculosis drugs, resistance to isoniazid was the most common (21%), followed by streptomycin (14%). MDR-TB was found in 15 cases (4.8%). Although the prevalence of TB in UAE is fairly low, an increasing number of cultures confirmed TB and MDR-TB among native and expatriate patients, necessitating improved vigilance in case detection, effective management and prevention of MDR and XDR-TB emergence in the country.