Tuberculosis is a major health problem worldwide. Genetic factors are considered important determinants of the host susceptibility to Mycobacterium tuberculosis. The aim of the current study was to evaluate the association between pentraxin 3 genetic variants and the susceptibility and severity of active pulmonary tuberculosis. The study included 100 patients with newly diagnosed pulmonary TB and 50 healthy controls. PTX3 plasma level was assayed using ELISA and PTX3 genotypes (rs2305619, rs3816527, rs1840680) were detected by real time PCR in all participants. PTX3 rs1840680 genotype (AA) and allele (A) were significantly higher in the study group while the genotype (GG) was higher in the control group. The plasma level of PTX3 was higher in the patients than controls (P<0.0001). There is a strong association between PTX3 plasma level and the activity and severity of pulmonary TB. PTX3 rs1840680 genotype AA is associated with increased risk of active pulmonary TB.