Methods of initializing an integrated circuit (IC) in which the routing structures have data lines and handshake circuitry are provided. A node of each of the data lines is driven to a predetermined value, and the handshake circuit is disabled by disabling an acknowledge path within the handshake circuitry, e.g., by forcing all acknowledge signals in the acknowledge path to signal an acknowledgement of received data. The disablement causes the predetermined value to propagate throughout the data lines. The handshake circuitry is then enabled by enabling the acknowledge path, which releases the data lines to assume values determined by operation of the IC. When the IC is a programmable IC, configuration values may be programmed into the IC after disabling the acknowledge path and before enabling the handshake circuitry. When the handshake circuitry is enabled, the data lines assume initial values determined by the programmed configuration values.