In its early years, helping to establish the Festival as a major international event were conductors Tullio Serafin and Nicola Rescigno, singers such as Ghena Dimitrova, Maria Chiara, Giuseppe Taddei, and Rolando Panerai, and well-known directors and set designers such as Giancarlo Menotti, Dinos Giannopoulos, Spyros Evangelatos, Nikos Georgiadis, Dionyssios Fotopoulos, and Nikos Petropoulos.
Soloists who have performed with the orchestra include Cecilia Gasdia, Ghena Dimitrova, Miriam Gauci, Joseph Calleja, Andrea Bocelli, José Carreras, Kate Aldrich, Daniela Dessi, and Lydia Caruana.
20th Century performers such as Nicolai Ghiaurov, Nicola Ghiuselev, and Ghena Dimitrova began their careers within the structure of the National Opera, as did later singers such as Irena Petkova.
Over the years numerous famous singers have sung on the Ruse opera stage: Elena Nikolai, Todor Mazarov, Nicolai Ghiaurov, Raina Kabaivanska, Nicola Giuselev, Anna Tomowa-Sintow, Ghena Dimitrova, Stefka Evstatieva, Orlin Anastassov, Valerie Popova, Gloria Lind, Alexandrina Milcheva, Vladimir Atlantov, Stefan Dimitrov, Ivan Konsulov, Ava Cooper, Peter Glossop, Zinaida Pali, Silvia Shash, Kaludi Kaludov, Mariana Zvetkova, Nicolae Herlia and many others.