After the overhaul of university education and research structures in the academic year 1998-1999, the Ruusbroec Institute became the Religious Sciences department. Following the departure of Jesuits Paul Verdeyen and Paul Mommaers, who retired in 2000 and 2001 respectively, new researchers were recruited. Veerle Fraeters, who had previously worked within the Dutch Literature department of UFSIA's Faculty of Germanic Philology, came to replace Fr. Verdeyen full-time in the summer of 2002. To fill the gap left by Fr. Mommaers in the autumn of 2003, church historian Theo Clemens (0,7 FTE) and Dutch philologist and theologian Rob Faesen s.j. (0,3 FTE) were taken on part-time. Meanwhile, the Ruusbroec Institute was renamed the 'Institute for the History of Spirituality in the Low Countries until c. 1750' when the three Antwerp university institutions (RUCA, UIA and UFSIA) merged to form the University of Antwerp (UA) on 1st October 2003. The new structure entailed a broadening of horizons with regard to research into spirituality, along with the assurance that the Institute's own independent research, as outlined by its founders, could continue unhindered. Around the time of the merger of the three Antwerp university institutions, Thom Mertens became the new Director of the Ruusbroec Institute and had to fulfill the difficult task of guiding the Institute through the changing academic landscape.
Three years after the merger, Fr. Guido de Baere retired at the end of September 2006. His retirement was celebrated with the completion of the critical edition of Jan van Ruusbroec's Opera Omnia. Kees Schepers, trained in literary theory at the University of Groningen, who had been working for the Institute as associate researcher since 1990, was appointed in his place with effect from 2007. In 2007 Frans Hendrickx, librarian of the Ruusbroec Institute Library since 1975, was succeeded by Erna Van Looveren, and under her care the library became member of the Flemish Heritage Library. Under the directorships of Theo Clemens and Thom Mertens the Ruusbroec Institute entered the second decade of the 21st century. After his retirement in 2012, Theo Clemens was temporarily succeeded by church historian August den Hollander (until September 2015).
2015, the year of the Institute's 90th anniversary, marked a new period in the history of the Ruusbroec Institute. For the first time in its history a female Director came to the helm of the Institute when Veerle Fraeters was chosen by the Institutional Board to fulfill this function. At the same time, Tine Van Osselaer, a specialist in religious history, along with her research team, brought changes to the Institute's mission. Their research of 19th and 20th-century stigmatics entailed a widening of the chronological scope of the Ruusbroec Institute from 1750 to the Second World War.
Four interdisciplinary colloquia were organized in order to celebrate the Institute's 90th anniversary: the so-called Ruusbroec Encounters. These encounters with scholars from Jewish Studies (IJS), Islamic studies (in cooperation with UCSIA), book historians (VWB) and researchers studying modern Flemish literature (ISLN) reached a wide and diverse audience, and received much positive feedback.