After his degree in 1966, he was post-doctoral fellow at the Mainz Academy of Sciences working with Pasqual Jordan, in Germany. Then, he was member of the Institute for Advanced Study, in Princeton and later became instructor and assistant professor at Princeton University. In 1975, he was visiting Professor at the Universities of Kyoto (Japan) and of Western Australia, Perth. In the years 1975-78, he cooperated with NASA being member of the task force on the scientific use of space stations. In 1976 he became Professor of Theoretical Physics at the University of Catania and in 1978 he was appointed Professor at the University “Sapienza”. In 1985, he was elected President of the International Center for Relativistic Astrophysics (ICRA)In 1984 he was cofounder, with Abdus Salam, of the Marcel Grossmann Meetings. In 1987, he became co-chairman of the Italian-Korean Meetings on Relativistic Astrophysics. In the years 1989-93, he was President of the Scientific Committee of the Italian Space Agency. He is Editor of a variety of Scientific Journals. He is married to Anna Imponente and has a son, Iacopo.

His theoretical workled to the concept of Boson Stars . His classical article with John A. Wheeler introduced for the first time the astrophysical concept of "Black Hole". With Demetrios Christodoulou he has established the reversible and irreversible transformations of a Black Hole and given the formula for a Kerr-Newmann Black Hole endowed of charge, mass and angular momentum. His theoretical work led to the identification of the first Black Holes in our Galaxy.

Together with his student C. Rhoades, he established the absolute upper limit to the mass of neutron stars and, with his student Robert Leach, he used such an upper limit for fixing the paradigm which enabled the identification of the first Black Hole in our Galaxy, Cygnus X1, using the splendid data of the Uhuru satellite by Riccardo Giacconi and his group ,.

For these works Ruffini won the Cressy Morrison Award of the N.Y. Academy of Science in 1972.

With his students Calzetti, Giavalisco, Song and Taraglio he has developed the role of fractal structures in Cosmology ,.

Together with his collaborator T. Damour, he suggested the applicability of the Heisenberg-Euler-Schwinger process of pair creation in Black Hole physics and identified the dyadosphere where these processes take place. Gamma ray bursts (GRBs) seem to give the observational evidence of such pair creation process in astrophysics, prior to the observation of such phenomenon in Earth based experiments and represent the first evidence of the energy extraction process from Black Holes (the blackholic energy).

He is co-author of 21 books, including:

• R. Giacconi and R. Ruffini, Physics and Astrophysics of Neutron Stars and Black Holes, LXXV E. Fermi Summer School, SIF and North Holland (1978); also translated into Russian
• R. Giacconi e Remo Ruffini, "Physics and Astrophysics of Neutron Stars and Black Holes" 2nd edition, Cambridge Scientific Publishers, Cambridge (2009)
• R. Gursky and R. Ruffini, Neutron Stars, Black Holes and Binary X Ray Sources, H. Reidel (1975)
• H. Ohanian and R. Ruffini. Gravitation and Spacetime, W.W. Norton (1994); translated into Italian (Bologna: Zanichelli, 1997) and Korean (Seoul: Shin Won, 2001)
• Bardeen, et al., Black Holes, Gordon & Breach (1973)
• M. Rees, et al., Black Holes, Gravitational Waves and Cosmology, Gordon & Breach (1974)
• H. Sato and R. Ruffini, Black Holes, Tokyo (1976)
• L.Z. Fang and R. Ruffini, Basic Concepts in Relativistic Astrophysics, Beijing: Science Press (1981)
• F. Melchiorri and R. Ruffini, Gamow Cosmology, North Holland Pub. Co., (1986)