The stability of trimethoprim-sulfamethoxazole (TMP-SMX) at various concentrations in 5% dextrose injection or 0.9% sodium chloride injection was studied. Appropriate volumes of TMP-SMX formulation (80 mg TMP and 400 mg SMX/5 mL) were mixed with 5% dextrose injection or 0.9% sodium chloride injection to provide dilutions of 1:25 v/v, 1:20 v/v, 1:15 v/v, and 1:10 v/v. Aliquots were removed at 0, 0.5, 1, 2, 4, 8, 14, 24, and 48 hours and filtered. The pH of the samples was determined, and the samples were assayed for trimethoprim and sulfamethoxazole content by high-performance liquid chromatography. Admixtures were visually inspected for precipitate before each sample was removed. The concentration of SMX in all admixtures did not change during the study period. The stability of TMP was dependent on concentration and vehicle. At a 1:25 v/v dilution, TMP was stable for 48 hours in 5% dextrose injection and 0.9% sodium chloride injection. At a 1:20 v/v dilution, TMP was stable for 24 hours in 5% dextrose injection and 14 hours in 0.9% sodium chloride injection. At a 1:15 v/v dilution, TMP was stable for four hours in 5% dextrose injection and two hours in 0.9% sodium chloride injection. At a 1:10 v/v dilution, TMP was stable for one hour in 5% dextrose injection and 0.9% sodium chloride injection. Concentrated solutions of TMP-SMX should be prepared in 5% dextrose injection, infused within one hour of preparation, and visually inspected for precipitation before and during infusion.