Cosmatos found success in Italy for directing the films "Rappresaglia" (1973) with Marcello Mastroianni and "The Cassandra Crossing" (1976) with Sophia Loren. In 1979, he made the successful British World War II adventure movie "Escape to Athena", starring an all-star ensemble cast including Roger Moore, David Niven, Telly Savalas, Elliott Gould and Claudia Cardinale. He made his North American directorial debut with the Canadian horror film "Of Unknown Origin". He then directed the box-office hit "" starring Sylvester Stallone, and "Cobra", another successful Stallone vehicle, in 1986. In 1989 he directed the science-fiction horror film "Leviathan", starring Peter Weller, Richard Crenna, Ernie Hudson, and Amanda Pays, with special effects designed by Stan Winston.