Pneumonia is a common manifestation of melioidosis, the disease caused by Burkholderia pseudomallei. In this study, we defined the prognostic significance of a positive sputum culture. A total of 712 patients presenting to Sappasithiprasong Hospital, Ubon Ratchathani, Thailand, with melioidosis between January 1992 and December 2002 had a sputum culture performed during admission, which was positive for B. pseudomallei in 444 patients (62%). The median duration of sputum positivity was 9 days (range, 1 to 49 days). Sputum cultures were negative in 32% of patients with radiologic changes suggestive of pulmonary involvement. Overall in-hospital mortality was 48%. A positive sputum culture was associated with mortality (adjusted OR 2.8, 95% CI: 1.9, 4.0; P < 0.001). This was independent of renal disease, a prior history of melioidosis, positive blood cultures, and other potential confounders. The presence of B. pseudomallei in the sputum of patients with melioidosis is associated with a poorer prognosis.