Background. Postoperative Mycoplasma hominis sternal wound or mediastinal infections are uncommon and difficult to diagnose. Atypical growth characteristics in routine bacterial culture, and the inability to demonstrate the organism on Gram stain, lead to delayed diagnosis of M hominis infections and increased morbidity. Methods. Postoperative purulent wound drainage or acute mediastinitis caused by M hominis developed in 3 cardiovascular surgery patients. These patients were considered along with 9 patients previously reported in the literature. Results. Operative findings included moderately thick, gray purulent fluid with the degree of tissue necrosis related to duration of infection. Intraoperative Gram stain of wound or mediastinal drainage demonstrated no microorganisms, and initial bacterial cultures did not reveal microbial growth. After an average of 4.5 days of culture, minute translucent colonies of M hominis were identified. The institution of appropriate antimycoplasma therapy (doxycycline and clindamycin) was associated with clinical or microbiological cure in all patients. Sternal wound complications developed in 3 patients, and a chronic infection developed in 1 patient. Conclusions. Empiric therapy for M hominis infection should be considered in patients with mediastinitis or a sternal wound infection in which organisms are not observed on Gram stain and are not readily cultured.