The ISO flange (also called Large ISO) is used for HV chamber ports and is available in two distinct styles; ISO-K which uses clamp fasteners and ISO-F which uses nut and bolt fasteners. A variety of bolt/clamp options permit joints between mixed ISO-K and -F flanges. The design principles of ISO and KF seals are identical. Each flange face is counter-bored or grooved to receive a metal centering ring with an elastomeric O-ring around its O.D. As with KF, the ISO centering ring both aligns the flanges and holds the O-ring in place.

ISO flanges are limited (by the O-ring's properties) to applications with temperatures between -0° C and 120-180° C, and pressure from atmosphere to -1010-8 mbar.