Objective: To observe and compare the clinical efficacy and safety of rifapentine and rifampicin in the treatment of tuberculosis. Methods: From January 2015 to January 2018, 398 tuberculosis patients admitted to Tuberculosis Clinic of the Traditional Chinese Medicine Hospital of Cixi were selected and randomly divided into observation group and control group by complete Random Distribution Method, with 199 cases in each group.The two groups were given basic treatments such as isoniazid, pyrazinamide and ethambutol.On this basis, patients in the control group were treated with rifampicin, and the observation group was treated with rifapentine.The treatment time of both two groups was 6 months.The sputum bacterial conversion rate, lesion absorption rate and cavity closure rate were observed, and the clinical treatment effect and adverse reactions were compared between the two groups. Results: The sputum bacteria conversion rate (77.89%), lesion absorption rate (71.86%) and cavity closure rate (74.87%) in the control group were significantly lower than those in the the observation group(96.98%, 91.96%, 95.98%) (χ²=31.03, 27.13, 35.60, all P<0.01). The total effective rate of the observation group was 93.97%, which was higher than 75.88% of the control group, and the difference was statistically significant (χ²=38.37, P<0.01). The incidence rate of adverse reactions in the observation group was 12.56%, which was significantly lower than 29.56% in the control group, the difference was statistically significant (χ²=17.59, P<0.01). Conclusion Compared with rifampicin, rifapentine is effective in treating pulmonary tuberculosis patients with high safety and effective improvement of clinical symptoms, which is worthy of further application.