The ruling released Wednesday comes a little more than a year after Douglas Prade was freed from prison based on new testing of a bite mark.
A judge in Akron ruled in January 2013 that new DNA test results proved Prade didn't kill his former wife.
The appeals court says the DNA testing only raised more questions than answers and that Prade's original conviction was based on a great deal of evidence.
Prade was convicted in 1998 of shooting his ex-wife to death where she worked as a doctor.
There were no witnesses and no fingerprints, and no gun was found.