Typhoid is a global problem. Conventional diagnostic methods have limitations. The Widal test gives a high proportion of false positive results, and indiscriminate use of antibiotics has reduced the utility of blood culture. Consequently, these procedures are inadequate for diagnosing suspected cases of typhoid that do not present clear-cut symptoms. We previously showed that PCR-based diagnosis of typhoid targeting the flagellin gene has unparalleled specificity. We assessed the utility of this method for diagnosis of problematic cases of typhoid. A comparative study of PCR, blood culture, and Widal test was carried out on 55 cases of suspected typhoid with fever for 3-30 days and possessing an ambiguous clinical picture. A control group comprised of 20 healthy persons was also included. The respective positive results by PCR, blood culture, and Widal test for these groups were 58.2 and 0%, 14.5 and 0%, and 52.7 and 45%. Sensitivity of PCR as compared with that of blood culture was significantly better. We concluded that PCR is much superior to conventional methods and, due to its high sensitivity and specificity, can be of great use for rapid and definitive diagnosis of problematic cases of typhoid.