A method and an apparatus for uplink transmission using multiple uplink carriers are disclosed. A wireless transmit/receive unit (WTRU) selects a dedicated channel medium access control (MAC-d) flow with highest priority data to be transmitted and performs uplink carrier selection and enhanced dedicated channel (E-DCH) transport format combination (E-TFC) restriction and selection to select a carrier among a plurality of carriers and select an E-TFC based on a maximum supported payload, a remaining scheduled grant payload of the selected carrier and a remaining non-scheduled grant payload. The WTRU then generates a medium access control (MAC) protocol data unit (PDU) for E-DCH transmission via the selected carrier based on the selected E-TFC.