The rebranded UEFA Cup competition is to feature an additional assistant referee beside each goal to help judge whether players have dived in the penalty box and committed fouls at set-pieces, and also determine if the ball has crossed the goal-line.
The system will be unveiled at 24 matches on Thursday with high-profile teams like Ajax Amsterdam, Valencia, AS Roma, Panathinaikos, PSV Eindhoven and Sporting Lisbon involved.
Officials are hoping it can drastically reduce the number of refereeing mistakes - often cruelly exposed by television replays - without using video technology.
UEFA president Michel Platini and FIFA counterpart Sepp Blatter are firmly opposed to technology, with the exception of microphones and headsets used by match officials to communicate with each other.
"Things have not improved in refereeing for more than 100 years. I am against video technology because that will take the human face away from the game but this system will help the referee make the right decision," Platini said last month.
"It could be the most significant change in the way the game is officiated for over 100 years."
The last major rule change came in 1992 when goalkeepers were banned from handling back passes following an outcry over negative play at the World Cup in Italy two years earlier.
BRAZILIAN EXPERIMENT
Nine years ago a low-key experiment was carried out in Brazil's Paulista championship where two match referees - one in each half of the field - took charge of games, each with equal responsibility.
However, soccer's governing body FIFA decided against adopting it.
The latest experiment was first tried in selected UEFA under-19 tournaments last year.
In February, football's law-making body the International Football Association Board (IFAB) said the experiment could continue at professional level.
The additional assistant referees will be positioned on the opposite side of the goal to the nearest linesman but will not have flags.
They will generally remain behind the goal but may enter the penalty area to keep up with the action when play moves to the other end of the pitch.
In the Europa League, they will be from the same country as the three other officials.
Technical experts appointed by the IFAB will monitor the referees' performances to assess the new system and determine whether they enhance their control of the match.
Manchester United manager Alex Ferguson said during a recent coaching forum the extra officials would also help at counter attacks.
"With the speed of the players today, it's impossible for the referee to keep up," he said. "It's progress and progress is important."
