Raonic hired American legend McEnroe as his new coach earlier this month and the pair are working together for the first time at the Wimbledon warm-up event in London.
McEnroe, a seven-time Grand Slam champion, has been putting Raonic through his paces on the practice courts at Queen's for several days and the early returns on their relationship look promising as the world number nine subdued the dangerous Kyrgios in a rain-interrupted first-round tie.
"You can't miss him. He has been on the court the whole time. I wanted to hit with some righties, but he is always there!" Raonic smiled when asked how he was finding life with the forthright McEnroe.
In contrast to Raonic, the controversial Kyrgios admitted recently that he is happy to go into Wimbledon without a coach. The 21-year-old, who has become notorious for his petulant on-court antics, has been able to call up Australian Davis Cup captain Lleyton Hewitt for advice.
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The deciding set was tight until Kyrgios lost his focus and served two successive double faults to gift Raonic a break in the ninth game.
Raonic looked like squandering the opportunity when he handed Kyrgios two break points as he served for the match, but he kept his cool and finished off the world number 19.
Del Potro returned to action in February after two years blighted by wrist problems and the former US Open champion decided the grass of Queen's and Wimbledon was a better bet for success than the Parisian clay.
However, Del Potro was unable to out-hit the towering Isner in a match-up of two of the ATP Tour's tallest players.
While Del Potro slipped and appeared to jar his knee several times, world number 17 Isner slammed down 25 aces as he booked a second-round clash with Luxembourg's Gilles Muller. Asked if 6ft 6in Del Potro was someone Isner looked up to as a fellow big server the 6ft 10in American laughed "Well, I look down on him still a little bit!
"He's one of our most popular players, without a doubt. Everyone in the locker room likes him. He's just a big chill dude."
British wildcard Kyle Edmund enjoyed the best win of his promising career as he defeated French world number 18 Gilles Simon 6-4, 3-6, 6-1. South Africa-born Edmund is ranked 85 and the 21-year-old's reward for shocking the eighth seed is a second-round meeting with France's Paul-Henri Mathieu, who defeated British wildcard Daniel Evans 7-6 (10/8) 6-7 (6/8) 6-3.