To date, there have been few studies on the dosage of fixed-dose combination (FDC) for the treatment of tuberculosis (TB) in the Chinese population. The aim of this study was to evaluate the efficacy and safety of two FDC regimens in two provinces with a high tuberculosis burden. A total of 2,353 newly diagnosed active pulmonary TB patients were recruited from Shandong Province (n=1,223) and Jilin Province (n=1,130). Participants received FDC treatment for six months (intensive phase and continuation phase). The difference in the two regimens was the dosage of FDC in the continuation phase. For Shandong Province, the cure rate was 96.4% (370/384). In all, 1,172 patients successfully completed the treatment, the success rate being 95.8% (1,172/1,223). For Jilin Province, the cure rate was 92.5% (345/373): 1,109 patients successfully completed the treatment and the treatment success rate was 98.1% (1,109/1,130). Significant differences were observed in the cure rate (X2=5.382, p=0.020) and the treatment success rate (X2=10.581, p=0.001) between the two provinces. The integral analysis showed that both regimens had similar efficacy, but the regimen of Jilin Province was inferior to that of Shandong Province in terms of safety.