Since linezolid was licensed, rare-but-serious adverse events caused by inhibition of mitochondrial protein synthesis have been identified. These events may be more common when the drug is used longer than 28 days, which is the treatment length currently approved by the US Food and Drug Administration. The purpose of this study was to determine how often longer courses of linezolid are prescribed and the nature and relative frequency of adverse events associated with longer courses. Most of the 460 infectious diseases physician respondents had prescribed extended course linezolid (greater than 28 days) at least once, and they reported that 74% of these patients were able to complete the extended course. Hematologic toxicity was the most common adverse event. Peripheral neuropathy and serotonin syndrome (with serotonin reuptake inhibitor use) were encountered more frequently than lactic acidosis. Close monitoring for signs and symptoms of these adverse events should be considered for patients receiving long-term therapy.