Abstract: Objective To understand the risk factors of drug-resistant tuberculosis in the city of Puyang and to provide the reference for the later the drug-resistant tuberculosis prevention and treatment. Methods We investigated and analyzed all the eligible smear—positive pulmonary tuberculosis patients in Puyang city from March 2010 to February 2013,among which 312 were drug-resistant tuberculosis patients and 426 were non drug-resistant patients. We analyzed the questionnaires including their diagnosis, the basic information of the patients, the present and the past medical records etc. Enumeration data was analyzed using χ² test. Difference with P<0.05 was consi-dered as statistically significant. Results The percentage of re-treatment patients in drug-resistant group and non drug-resistant group were respectively 27.9% (87/312) and 15.0% (64/426), and the comparison between two groups was χ²=18.42, P<0.01; the completion rate of their first anti-tuberculosis treatment course in two groups of patients were 65.5% (57/87), 92.2% (59/64) respectively, and the comparison between two groups was χ²=14.73, P<0.01;the proportions in the two groups of patients with lesions involving the lung field ≥3 were respectively 55.1% (172/312), 18.8% (80/426), the comparison between two groups was χ²=105.82, P<0.01; the rates in two groups of patients with lung cavity were 31.7% (99/312), 12.2 % (52/426), the comparison between two groups was χ²=42.18, P<0.01. The detection rates of patients with drug resistance in Puyang city, Puyang county, Qingfeng county, Nanle county, Fanxian county, Taiqian county accounted for 37.4% (79/211), 67.3% (74/110), 41.2% (66/160), 39.9% (55/138), 57.4% (35/61), 51.7% (30/58); the comparison between Fan-xian county and the city of Puyang city was χ²=7.73, P<0.01; the comparison between Fan county and Qingfeng county was χ²=4.63, 0.01＜P<0.05; the comparison between Fan county and Nanle county was χ²=5.24, 0.01＜P<0.05; the comparison between Taiqian county and Puyang city was χ²=3.85, 0.01＜P<0.05. Conclusion Based on investigation and analysis of 738 cases in Puyang city, the results indicated that the re-treatment patients, the first anti-tuberculosis treatment completion in re-treated patients, lesions involving the lung field ≥3, patients with cavity are high risk factors of drug resistance pulmonary tuberculosis in Puyang area, the high incidences of pulmonary tuberculosis occurred in Taiqian county and Fan county region.