Pagliuca was born in Bologna. In his club career, he played for Sampdoria (1987–94), Internazionale (1994–99), Bologna (1999–2006), and Ascoli (2006–07). His most notable successes with Sampdoria include one Cup Winners' Cup and one "Scudetto"; he also reached a UEFA Champions League final, losing 1–0 to Barcelona in 1992, at Wembley, in spite of his impressive performance.