||Objectives-To investigate effects of needle and catheter size on in vitro ultrasound contrast agent (UCA) enhancement and concentrations using 4 commercially available UCAs. Methods-Definity (Lantheus Medical Imaging, North Billerica, MA), Optison (GE Healthcare, Princeton, NJ), SonoVue (Bracco SA, Geneva, Switzerland), and Sonazoid (GE Healthcare, Oslo, Norway) were investigated. The UCA was injected via a 1-mL syringe (BD, Franklin Lakes, NJ) into a 3-way stopcock (Smith Medical, Dublin, OH) and flushed with 10 mL of saline through an 18-cm infusion extension tube connected to either a 16-, 18-, 20-, 22-, or 24-gauge catheter (BD) or an 18-, 20-, 21-, or 25-gauge needle (BD). In vitro enhancement was determined in a flow phantom (ATS Laboratories, Bridgeport, CT), and microbubble concentrations were determined using an LSRII flow cytometer (BD Biosciences, San Jose, CA). Results-Significant decreases in enhancement and microbubble concentrations were observed for all 4 UCAs (P < .001) when administration was performed through a 25- gauge needle. No statistically significant differences in enhancement or concentrations were observed between all catheter sizes and 18- To 21-gauge needles for SonoVue and Sonazoid. Definity and Optison administration through a 24-gauge catheter resulted in a significant loss of enhancement (P < .02), although these differences were not significant on flow cytometry. Conclusions-Administration of commercial UCAs in a clinical scenario is possible with catheters or needles smaller than 20 gauge, although the minimal allowable size appears to be UCA specific. © 2015 by the American Institute of Ultrasound in Medicine.