Blockage of nasoduodenal feeding tubes is costly in terms of materials and nursing time, and traumatic to the neuroscience patient. A laboratory experimental study explored ways to decrease obstruction of small bore nasoduodenal feeding tubes when medications are given concurrently with continuous tube feeding. The first part of the study examined type and form of 4 medications in relation to frequency and timing of tube blockage. Trimethoprim sulfamethoxazole (Septra) in dissolved pill form blocked tubes most frequently (F10,77 = 10.333, p < .001) and in the shortest time (F10,77 = 10.534, p < .001). The second part of the study examined different irrigation methods. Irrigation before and after administration of medication and irrigation after medication administration only were significantly better than no irrigation in preventing blockage, both in terms of number of occlusions (F2,87 = 5.486, p < .01) and time to occlusion (F2,87 = 4.556, p < .02). The fact the study was performed in vitro rather than in vivo was a limiting factor. However, results of the study suggest trimethoprim sulfamethoxazole forms occlusions, especially in dissolved form. Elixir of this medication should probably be used whenever available. This study also found that irrigating the tube before and after administration of medications was the most effective of the 3 options examined.