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In this paper, we theoretically investigate the sensitivity enhancement of nanowire-based surface plasmon resonance (SPR) biosensors using rigorous coupled-wave analysis (RCWA). For a higher sensitivity, we are particularly interested in the size, period, and geometry of gold nanowires. When the nanowire period is less than 300 nm, the calculated sensitivity enhancement of a nanowire-based SPR configuration is more than ten-fold compared with that of a conventional one. Moreover, for a reliable performance, we study a modified SPR structure with periodic patterns of nanowires deposited onto a gold film. In such a schematic of nanowire-enhanced SPR biosensor, the sensitivity enhancement induced by nanowires with a T-profile is better than that of nanowires with an inverse T-profile.