Pulmonary infection by Mycoplasma hominis (M hominis) in lung transplant (LTx) recipients is an uncommon yet potentially severe complication. Bronchial dehiscence in the context of M hominis infection has not been previously reported. In this report, we discuss a case of donor-derived M hominis infection in a LTx recipient with bilateral bronchial anastomoses dehiscence and stenosis. The infection was managed using a multidisciplinary approach: repeat surgical revision of the necrotic anastomosis; targeted antibiotic therapy with the combination of oral and inhaled fluoroquinolones, and oral doxycycline and continuous ventilatory support. Response to therapy was monitored through repeat bronchoscopy and serial quantitative PCR assays for M hominis in bronchoalveolar lavage and aspiration. The rare nature of M hominis infection after LTx, its difficult detection in conventional cultures and innate resistance to beta-lactams make diagnosis and timely treatment of this organism challenging. We recommend that transplant centers have a low threshold for screening for Mycoplasma infection, particularly in patients with unsatisfactory postoperative course and little response to broad-spectrum antimicrobial and antifungal coverage. Monitoring with PCR may help to adapt the duration of antibiotic therapy.