Introduction The diagnosis of tuberculous (TB) pleurisy remains difficult because of its paucibacillary character. Several authors have studied the usefulness of interferon gamma release assays in the early diagnosis of TB pleurisy, whereas these tests are designed for the detection of latent TB infection. Our objective is to study the performance and clinical relevance of QuantiFERON TB Gold in Tube (QFT-GIT) in the diagnosis of TB pleurisy in Algeria. Patients and methods QFT-GIT was tested in vitro in serum and pleural fluid on a prospective recruitment of 158 immunocompetent patients with pleural effusion. Results Of the 158 cases of pleurisy identified, 84 (53.84%) were TB, diagnosed and proven by conventional methods, and 72 (46.15%) were non-TB, of whom 67 (93%) were confirmed of neoplastic origin, five (7%) secondary to a systemic disease and two of nonspecific inflammatory origin. Our results showed a high pleural sensitivity of QFT-GIT (97.62%) compared to serum sensitivity (80.95%). In contrast, serum specificity (83.78%) was higher than pleural specificity (72.97%). When we used the optimal values from the receiver operation characteristics curve analysis, the area under the curve of interferon-gamma produced by the QFT-GIT test was significantly higher in the pleural fluid than in the blood. Area under the curve of TB antigen interferon-gamma response was 92, 18 [95% confidence interval (CI)=87.56–96.79], nil tube was 95.71% (95% CI=92.43–99), and mitogen tube was 65.34 (95% CI=57.71–72.98). Conclusion QFT-GIT in pleural fluid appears in our study as a useful test for the diagnosis of TB pleurisy, but its diagnostic accuracy needs to be validated in further large-scale research.