The objectives were to define the incidence, risk factors, clinical features and outcome of arterial desaturation syndrome following talc pleurodesis in patients with malignant pleural effusions. This retrospective, observational study took place at a tertiary care cancer center in New York. All patients were those with malignancy who underwent pleurodesis with talc in 1998 at Memorial Sloan Kettering Cancer Center. Characteristics of patients are described by using summary statistics. Differences between groups were assessed with the Fisher's exact statistic for categorical variables and Student's t-test for continuous variables. Among patients who were considered to have arterial desaturation syndrome, we evaluated the relation of SaO2/FIO2 pre- and post-talc installation using a paired Student's t-test. During 1998, 120 patients underwent pleurodesis with talc, and 8 (7%) developed arterial desaturation following the procedure. Symptoms included chest pain, dyspnea, fever, and increased need for oxygen supplementation developed typically within 1 day. Three of the eight patients in this series required mechanical ventilation, but all recovered uneventfully after treatment, which included high-dose corticosteroids. Patients with breast and ovarian cancer appeared to be at increased risk for this complication compared to those patients with other types of cancer (p = 0.01). Approximately 7% of patients who have undergone sclerosis with talc for a malignant pleural effusion will develop arterial desaturation with clinically significant hypoxia requiring supplemental oxygen following the procedure. It appears that most patients recover from this complication and that those with breast and ovarian cancer may be at higher risk.