BACKGROUND: Insulin pump users experience periods of unexplained hyperglycemia. In some cases these may be due to insulin flow interruptions termed "silent occlusions," which occur without activating the pump alarm and may require set replacement. MATERIALS AND METHODS: In-line pressure profiles of a novel infusion set with a 6-mm, 28-gauge polymer, dual-ported catheter (BD FlowSmart™; Becton Dickinson and Co., Franklin Lakes, NJ) were compared with those of an existing infusion set (Quick-set®; Medtronic MiniMed, Northridge, CA) in two separate studies involving insulin diluent infusions over 2.5-4.5-h periods in healthy adults without diabetes. Study 1, a pilot study (n = 25), compared the occurrence of flow interruption events (silent occlusions and/or occlusion alarms) between the two infusion sets and between manual or device-assisted insertion methods. Study 2 (n = 60) was designed to show ≥50% reduction in flow interruption events with the BD set after manual insertions. (Silent occlusions were defined by a continuous pressure rise for ≥30 min.) RESULTS: In Study 1, significantly fewer silent occlusions were seen with BD FlowSmart versus Quick-set infusion sets for both manual (three of 22 [13.6%] vs. 12 of 24 [50%]; P = 0.012) and mechanical (two of 24 [8.3%] vs. nine of 25 [36%]; P = 0.037) insertions, yielding risk reductions of 73% (95% confidence interval [CI], 25-91%) and 77% (95% CI, 17-94%), respectively. In Study 2, flow interruption events occurred in three of 117 (2.6%) and 12 of 118 (10.2%) BD FlowSmart and Quick-set infusion sets, respectively, yielding a 75% risk reduction (95% CI, 20-92%; P = 0.030). Percentage of time with flow interruption was significantly lower with BD sets in both studies (P < 0.02). Leakage (>0.5 IU or 5 µL) occurred infrequently and did not differ between sets. CONCLUSIONS: A novel side-ported insulin infusion set demonstrated significant reductions in flow interruptions, including silent occlusions, versus a leading marketed set, which may improve insulin delivery.