Inexpensive nitric oxide (NO) release strategies to prevent thrombosis and bacterial infections are desirable for implantable medical devices. Herein, we demonstrate the utility of electrochemically modulated NO release from a catheter model using an inner copper wire working electrode and an inorganic nitrite salt solution reservoir. These catheters generate NO surface fluxes of >1.0×10−10 mol min−1 cm−2 for more than 60 h. Catheters with an NO flux of 1.1×10−10 mol min−1 cm−2 are shown to significantly reduce surface thrombus formation when implanted in rabbit veins for 7 h. Further, the ability of these catheters to exhibit anti-biofilm properties against bacterial species commonly causing bloodstream and urinary catheter infections is examined. Catheters releasing NO continuously during the 2 d growth of S. aureus exhibit a 6 log-unit reduction in viable surface bacteria. We also demonstrate that catheters generating NO for only 3 h at a flux of 1.0×10−10 mol min−1 cm−2 lower the live bacterial counts of both 2 d and 4 d pre-formed E. coli biofilms by >99.9%. Overall, the new electrochemical NO-release devices could provide a cost-effective strategy to greatly enhance the biocompatibility and antimicrobial properties of intravascular and urinary catheters, as well as other implantable medical devices.