Background Macrophage migration inhibitory factor (MIF) makes chemokine-like functions and plays critical roles in various inflammatory diseases. This study was designed to explore the significance of MIF serum levels in predicting the prognosis of pulmonary tuberculosis (PTB) following anti-TB treatment. Methods Patients diagnosed with culture-confirmed PTB without treatment were included and the serum was collected. Levels of MIF in serum were quantified with immunoassay, and the levels of established biomarkers were also determined, including C-reactive protein (CRP) and Interleukin 6 (IL-6). The outcome was estimated with all-cause mortality, with the mortality in 12 months as the primary outcome and the mortality in 3, 6, 9 months as other outcomes. The prognostic value of MIF and other factors in PTB were tested. Results Two hundred eighty-seven PTB patients were included. The median MIF levels in patients with advanced disease, disseminated and drug-resistant TB were significantly higher than that observed in mild -to- moderate disease, non-disseminated and drug-sensitive TB. MIF levels in patients with the outcome of death were higher than those survived [28.0 ng/ml (Inter-quartile range [IQR]: 24.2–33.1) vs. 22.3 ng/ml (IQR: 18.7–26.5); P < 0.001]. Multivariate model analysis was performed for comparing the highest quartiles to the lowest quartile of MIF levels. MIF levels were related to the mortality, with an elevated mortality risk of 236% [Odds ratio (OR) = 3.36; 95% Confidence interval (CI): 1.21–15.14; P = 0.012]. The model was re-analysis after combing MIF with currently established risk indicators. The obtained Area Under the Receiver Operating Characteristic Curve (±standard error) was elevated from 0.81 (±0.035) to 0.84 (±0.031), with a significant difference before and after adding the MIF (difference, 0.03[0.004]; P = 0.03). Conclusion Serum level of MIF was a better biomarker than CRP or IL-6 for predicting death in HIV-negative PTB patients, and increased MIF serum levels were related to higher mortality.

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