Ronaldo's record 80 million pound transfer to Real Madrid was seen by some as the first in a flood of top players leaving England, now less attractive because of the weak pound and new higher top rate of income tax.
Scudamore, however, compared the Portuguese forward's exit to the 2003 departure of another Manchester United player who joined Real, David Beckham.
"I remain entirely phlegmatic because I know the game will sustain any one player moving either way," he said in an interview during the Premier League's recent Asia Trophy in Beijing.
"It's always exciting when a new one arrives, but players leave. As long as we've got some stars - and we've got lots - the individual one itself doesn't matter.
"If, over time, a hundred Cristiano Ronaldos left in two seasons and we had nobody, I might be sitting here with a different perspective.
"Let's talk again on September 1 when the transfer deadline closes. We'll have lost a couple but we'll have gained a couple too."
It is not just bringing in top names that will fill the gap left by Ronaldo and Xabi Alonso, who has left Liverpool for Real, Scudamore said.
"They are stars now that you've heard of them, but there are people that you haven't heard of that in three, five years' time will have come up through the ranks and will replace them."
For a man who leads a league whose 20 clubs had combined debts of 3.1 billion pounds even before the global economic downturn, Scudamore is upbeat about the financial future.
"I think we are quietly pleased the way we've managed over the last 18 months," he said.
"The clubs have shown flexibility with ticket pricing which has kept the stadiums full and it looks like season ticket sales for next season have held up extremely well."
The main reason for his optimism, however, is that the domestic TV rights for the next four seasons are already sold, mostly to pay-TV firm BSkyB.
FIVE PERCENT RISE
The league said in February that the auction of rights for the three seasons from 2010-11 to 2012-13 had secured them 1.78 billion pounds, five percent up on the previous deal.
"The domestic TV deal is most important, it's still three quarters of what we do economically," he said.
"And to get that away at a slightly increased level was huge. That takes us through four years, and everyone's predicting we should be out of this current slump in a couple of years so therefore, that takes us past that.
"Internationally, we were hedged in many ways as we're not taking huge amounts from any one country," he added.
"If you take a little bit from each country, some will be doing well, some not, so you're hedged a bit. I think we are in a good position to weather the (economic crisis)."
The Premier League season starts on Saturday.
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