The median price for San Diego single-family resale homes, based on National Association of Realtors data, was reported at $469,000, compared with San Francisco's $706,300, which made it the least affordable on the list.
Using household incomes, the report listed San Diego as 24th in affordability and San Francisco in last place.
San Diego's median income was listed at $60,330, ninth highest on the list, while San Francisco was first at $74,922.
The most affordable city was Atlanta, where the median home price is $143,300 and median income, $54,628. Runners-up in affordability were Minneapolis, St. Louis, Detroit and Pittsburgh.
Mike Sante, managing editor of Income.com, said the study shows that incomes are not keeping up with recovering home prices.
"The simple fact is that the very small improvement Americans have seen in their paychecks hasn't kept pace with a jump in home prices and mortgage rates," he said.