Next is continuing to prosper despite constrained consumer incomes with a 12% rise in pre-tax profit to £695 million for the year to January 2014, at the top end of City expectations, putting it on track to overtake Marks & Spencer in annual earnings.
Lord Wolfson said of independence: "I don't think it would make any difference.
"We manage our business in Eire how we manage in the UK.
"We do not see Scottish independence as a business issue."
The chain has around 40 stores in Scotland out of a total of 500 outlets in Britain and Ireland plus 200 outlets overseas. It also has the increasingly important Next Directory internet and catalogue business.
The position of Lord Wolfson, who has Scottish connections through his great-grandfather, Solomon Wolfson, a Polish cabinet-maker who settled in Glasgow, is in contrast to a number of food retailers who have indicated that they would find trading in an independent Scotland more expensive which could lead to price rises.
Next benefited from soaring online sales, up 12.5% to £1.3 billion during the year, which added £48m to annual profits. Sales in its stores rose 1.7% to £2.2bn, but it would have fallen without the contribution of new space as customers moved to internet shopping.
The company is guiding the City towards profit growth of 5% to 11% next year and total shareholder returns of 10% to 16% including dividends.
Lord Wolfson acknowledged that falling real incomes are being supplemented by consumers borrowing more and that a hiatus in credit growth, in the absence of a pick-up in wages, could hit the sector.
"The fact is that real incomes may not grow. If that happens we cannot expect growth in the credit market to bail us out," he said.
"As the economy gains strongly interest rates will have to go up. That will have the effect of dampening the economy. Any recovery we get is not likely to be dramatic in terms of consumer spending."
He acknowledged that City analysts are correct to identify Next as one of the retailers most exposed to rising interest rates due to its customer base of 25-40 year olds with sufficient incomes to be home owners but without the maturity to have paid down their debt. Many other chains cater to younger shoppers yet to get onto the housing ladder.
"I think Next is more vulnerable to [the effects of] an interest rate rise than much of the market particularly young fashion," he said.
Next's profit surge means its annual profits are likely to be ahead of long-time market leader Marks & Spencer which is expected to bring in £615m as it struggles to maintain its market share.
Lord Wolfson said he does not focus on what rivals are doing.
"What matters is not our relative performance," he said. "Shareholders are not rewarded by us being the biggest."
Store growth in the coming year will include a large proportion of Home stores which are benefiting from greater activity in the property market.
Lord Wolfson insisted that the current house price boom is sustainable with transactions at a lower level than for much of the last 20 years.
Next is benefiting from continuing weak conditions in commercial property. Lord Wolfson said that most of its sites continue to see no rent rises or falling rents.
Next's shares closed up 150p or 2.3% at 6,730p.