Introduction The FDA issued a warning on the increased risk of hematologic relapse based on the ALLOZITHRO trial, recommending azithromycin not be used long-term in patients that have undergone allogenic hematopoietic stem cell transplant (HSCT). In the ALLOZITHRO trial, azithromycin was started at the time of the conditioning regimen for prophylaxis of bronchiolitis obliterans (BO); however, at our site and many others across the country, azithromycin is initiated after BO. Objective The goal of this study was to evaluate if azithromycin used in treatment of BO is associated with an increase in the rate of relapse. Methods IRB approval was obtained prior to review of the electronic medical record and the Mayo Clinic HSCT database. Adult patients who received an allogeneic HSCT from January 2008 – August 2018 for a malignant disease and received ≥ 2 weeks of azithromycin were included in this study. Patients were excluded if they received <2 weeks of azithromycin therapy, received azithromycin prior to 100 days post-HCST, relapsed prior to the initiation of azithromycin, or never achieved disease remission prior to starting azithromycin. Data collected via retrospective review included patient demographics, azithromycin regimen and duration, death, relapse, and date of last follow-up. Results Of 466 adult patients who received an allogenic HSCT at Mayo Clinic Hospital-Rochester for malignant disease, 185 patients received azithromycin. Of 185 patients who received azithromycin, 87 were excluded: declined research participation (n = 7), received <2 weeks of azithromycin therapy (n = 65), azithromycin initiated prior to 100 days post-HCST (n = 11), relapse prior to the initiation of azithromycin (n = 2), or never achieved disease remission (n = 2). We identified 98 patients who met our inclusion/exclusion criteria. The median age was 56 years (23-74). The majority of patients received azithromycin 250 or 500 mg three times weekly: 500 mg three times weekly (n = 51), 250 three times weekly (n = 40). The median time to azithromycin initiation was 16.6 months (IQR 9.4-26). The median duration of azithromycin therapy was 33.9 months (IQR 1.4-116.4). Death occurred in 2 patients (2%) and was not related to relapse. Two patients (2%) relapsed a median of 28 months (IQR 7.2-49) after transplant. The median time to relapse after azithromycin initiation was 10.4 months (IQR 2.5-18.2). The two patients who relapsed were at high risk for relapse as one had FLT3 ITD mutation in CR1 without FLT3 inhibitor treatment, and the other had heavily pretreated multiple myeloma. Both achieved remission and are alive at the time of last follow up. The median overall survival for this cohort from the start of azithromycin was not reached. Conclusion The use of azithromycin as treatment for BO was not associated with a high incidence of disease relapse in this study. Further research is needed to confirm our findings. [ABSTRACT FROM AUTHOR]