ABSTRACT Background: Diagnosing TB is a particular challenge among HIV infected individuals, who are more likely to have smear-negative pulmonary TB. Microscopy has low sensitivity, specificity and predictive values in HIV patients. XpertMTB/RIF has recently been introduced in Tanzania to facilitate early diagnosis. Objectives: The aim of this study was to optimize the current Tanzania TB diagnosis in HIV co-infection using XpertMTB/Rif. This study has characterized TB features in HIV co-infection and then assessed the sensitivity, specificity and positive and negative predictive value of XpertMTB/Rif for TB detection in symptomatic and asymptomatic HIV patients, compared to microscopy using culture LJ as a gold standard. Methodology: This was a cross-sectional analytical study, which was conducted at Kibong’oto Hospital HIV clinic, with 69 participants. Demographic, clinical, laboratory and radiological data were collected. Then performance of XpertMTB/RIF and Microscopy using LJ (Lowenstein Jensen) culture as a gold standard were determined. Results: All of the TB infected HIV patients had at least a single TB cardinal symptom. No asymptomatic patient was diagnosed with TB. Low CD4 count was the only predictor of positive XpertMTB/Rif. XpertMTB/Rif had higher sensitivity (100%), specificity (100%), PPV (79.2%) and NPV (98.9%) as compared to microscopy. It also had higher sensitivity (100%), specificity (100%), PPV (76.5%) and NPV (98.9%) as compared to microscopy among the symptomatic patients. Discussion: Using clinical TB symptoms alone as screening tool in HIV infected individuals may results in to overtreatment of TB in this population. On the other hand relying on Microscopy alone for TB screening in HIV patients has the potential of TB under-diagnosing and miss-diagnosing. Differences in CD4 levels among HIV patients and variability in radiographic reading and interpretations might affect chest x-ray TB predictive capacity. Depletion of antigen-specific interferon gamma (IFNγ) producing CD4 T-lymphocytes increases risk of TB development and progression. The study validates the active use of XpertMTB/Rif in early detection of TB among HIV patients, as compared to the use of Microscopy which might lead to under-diagnosis, misdiagnosis and delayed treatment. Conclusion: XpertMTB/Rif correctly detected all culture positive TB cases among HIV patients, and correctly detected as negative those with negative TB by culture. XpertMTB/Rif should continue to be used for the early detection of TB among HIV patients as it has higher performance compared to microscopy. Keywords: XpertMTB/Rif, Tuberculosis, Diagnosis, Role, Optimizing, Tanzania, HIV