The study aimed to identify risk factors for multidrug-resistant tuberculosis (MDR-TB) among Afghan immigrant patients at a tertiary care hospital in Iran. This was a retrospective analysis of all confirmed Afghan immigrant TB patients from December 2000 – June 2005. Drug susceptibility testing (DST) to isoniazid, rifampicin, streptomycin, ethambutol, and pyrazinamide was performed on Lowenstein–Jensen media according to proportion method. The risk factors associated with MDR-TB were investigated. Mycobacterium tuberculosis strains were isolated from 668 Afghan immigrant patients. There were 397 males and 271 females and the mean age was 35.2 ± 16.3 (SD). Based on DST, Afghan immigrant patients were divided into two groups: 493 patients were non-MDR and 175 patients were MDR-TB. The variables significantly associated with MDR were under 45 years of age, male sex, previous TB treatment, poor socio-economic conditions, and smoking. Site of TB disease whether pulmonary or extra-pulmonary, and drug abuse habit were not associated with MDR TB. In conclusion, based on our results an improved TB control programme, which must be coupled with early detection of MDR-TB among Afghan immigrant patients particularly in those with high risk factors, is highly recommended.