Compared with the treatment of drug-sensitive tuberculosis, the treatment of multidrug-resistant tuberculosis (MDR-TB) is more difficult. This study was conducted at the national referral center of tuberculosis in Tehran, Iran, to evaluate adverse drug reactions of treatment of MDR-TB. From 2006 to 2009, all patients admitted into Masih Daneshvari Hospital in Tehran, Iran, for MDR-TB were considered for this study. The standard treatment for MDR-TB consisted of amikacin, prothionamide, ofloxacin, and cycloserine. Ethambutol and pyrazinamide were added to treatment if mycobacterium was sensitive to them. All adverse effects observed in patients were recorded in our registry. Eighty patients were considered in the study; of this cohort, 44 were male and 36 were female. The mean age of patients was 40.64 ± 17.53 years (range, 14-81 years). All patients received standardized therapy for MDR-TB. The major adverse effects included neurologic side effects (depression, convulsions, consciousness, psychosis, suicide; 7.5%), hepatitis (5%), rash (1.3%), renal toxicity (3.8%), and auditory toxicity (14.5%). Those with neurologic side effects had less favorable outcome (P value = 0.038) and risk of death was increased among them (odds ratio, 13.8; 95% confidence interval, 2.2-86.77). Other adverse effects did not show statistical significance in our analysis. A major adverse effect such as neurologic side effects (depression, convulsions, consciousness, and psychosis) can result in an increased chance of death among patients with MDR-TB.