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Effects of Sulfamethoxazole-Trimethoprim on Airway Colonization with Pneumocystis jirovecii. Reactivation of latent infection is considered to be the main mechanism underlying the development of Pneumocystis pneumonia in immunosuppressed patients. We retrospectively assessed the effects of prophylactic administration of sulfamethoxazole-trimethoprim on the development of P. pneumonia and airway colonization with P. jirovecii in patients undergoing examinations to diagnose or rule out P. pneumonia. Polymerase chain reaction was performed to detect P. jirovecii in bronchoalveolar lavage fluid or sputum of 60 consecutive patients between 2004 and 2012. No patients who received the prophylactic administration of sulfamethoxazole-trimethoprim (n = 10) developed P. pneumonia or demonstrated airway colonization with P. jirovecii, and none of the patients who developed P. pneumonia (n = 11) or showed colonization (n = 9) had received prophylactic treatment. Furthermore, 20 (40%) of 50 patients without prophylactic treatment showed positive results on the P. jirovecii DNA polymerase chain reaction, but all 10 patients who had prophylactic treatment showed negative results (Fisher's exact test, P = 0.02). Therefore, the prophylactic administration of sulfamethoxazole-trimethoprim has potential to be effective in preventing P. pneumonia as well as eliminating airway colonization with P. jirovecii. Further studies targeting large cohorts of patients with a variety of underlying diseases are required to develop recommendations regarding the prophylactic administration of sulfamethoxazole-trimethoprim.