Stenotrophomonas maltophilia is a gram-negative bacterium that has been cultured with increasing prevalence from the sputum of patients with cystic fibrosis (CF). We conducted a cohort study, using the Cystic Fibrosis Foundation Registry, to assess the effect of S. maltophilia on survival. We studied all patients in this registry from 1991 to 1997 who were older than 6 years of age, were S. maltophilia negative in the first year of enrollment, and had their CF diagnosed before the age of 45 years (n = 19,255 in the study). We compared patients who acquired S. maltophilia with those who did not, using survival analysis. A total of 1,673 (8.7%) had at least one sputum sample positive for S. maltophilia. Compared with patients without S. maltophilia, those patients positive for S. maltophilia had the following baseline characteristics before detection: lower FEV(1) % pred (p < 0.001); older (p = 0.001); more likely to be female (p = 0.003); and more pulmonary exacerbations (p < 0.001), outpatient visits (p < 0.002), and total hospitalizations (p < 0.001). After controlling for differences in severity of disease and coinfection with Pseudomonas aeruginosa, the hazard ratio associated with S. maltophilia detection was 0.89 (95% confidence interval, 0.75-1.05). Although patients with CF who acquire S. maltophilia have more advanced disease than those who do not acquire this organism, detection does not independently affect short-term survival (3 years).