To clarify the clinical presentation and course of patients with spontaneous pneumomediastinum (SP) and to determine the usefulness of diagnostic testing in these patients. We conducted a retrospective review of 62 consecutive adult patients (age >or=18 years) diagnosed as having SP during an 11-year period from July 1, 1997, to June 30, 2008. The study cohort included 41 men and 21 women (median age, 30 years; interquartile range, 20-69 years). Among the 62 study patients, the most common presenting symptoms were chest pain (39 patients [63%]), cough (28 [45%]), and dyspnea (27 [44%]). Preexisting lung diseases were identified in 27 patients (44%) and included interstitial lung disease, asthma, lung malignancies, bronchiolitis obliterans syndrome, chronic obstructive pulmonary disease, bronchiectasis, and cystic lung lesions. The initial diagnosis of SP was achieved by chest radiography in 52 patients (84%); the remaining cases were diagnosed by computed tomography. Forty-seven patients (76%) were hospitalized for a median duration of 2.5 days. Additional diagnostic procedures were performed in 27 patients (44%) and included contrast esophagography, bronchoscopy, and esophagogastroduodenoscopy; however, they did not yield a pathologic cause in any patient. Pneumothorax was identified in 20 patients (32%), but less than one-third of these patients underwent chest tube thoracostomy. No episodes of mediastinitis or sepsis occurred. Recurrence of SP was seen in 1 patient, and thoracoscopic surgery was performed in 1 patient for persistent air leak (pneumothorax). Spontaneous pneumomediastinum was associated with a relatively benign clinical course; however, pneumothorax was seen in 32% of cases. Diagnostic testing to determine a pathologic cause yielded little clinically relevant information in these patients.