Background : Tuberculous pleural effusion (TPE) occurs in up to 25% of TB patients. Owing to the pauci-bacillary nature of the pleural fluid, the diagnosis of TPE is a challenge. Newer diagnostic tools are required for the rapid diagnosis of TPE. Objectives : To compare the sensitivity and specificity of Xpert MTB/RIF and Geno type MTBDRplus line probe assay (MTBDRplus) for diagnosing TPE.  Methods : A prospective cross-sectional study was performed at Aga Khan University Hospital, Karachi, Pakistan from August 2014 to January 2016. Patients with suspected TPE were recruited on the basis of history, exudative lymphocytic nature of effusion and raised adenosine daminase level. Pleural fluid samples were tested for AFB smear, culture, Xpert MTB/RIFand MTBDR plus . Results :  We enrolled 99 patients with mean age of 50.4±20.3 years. AFB culture was positive in 14 (14.14%) cases. Considering AFB culture as Gold standard, the sensitivity of Xpert MTB/RIF was found to be 57.14% (95% CI: 28.86 – 82.34%) and specificity was 97.65% (95% CI: 91.76 - 99.71%) and the sensitivity of MTBDR plus  was  35.71% (95% CI: 12.76 – 64.86%) and specificity was 98.82% (95% CI: 93.62 - 99.90%).The sensitivity of Xpert MTB/RIF in TPE was higher than MTBDRplus (p 0.013), while specificity was similar. Conclusion :  Xpert MTB/RIF is more sensitive for detecting TPE than MTBDRplus and AFB smear microscopy. A multicenter, large-sample study is needed to evaluate this method for early TPE diagnosis.