Compton was tied for 13th going into the final round at Southern Hills Plantation Club, but had two bogeys in the opening three holes and never quite caught up. He was even at the turn, but bogeyed the 15th and finished with three pars for a 6-under 282 to tie for 22nd.
Only the top 20 and ties advance to the final stage of Q-school next month in California.
Todd Demsey, who returned to the PGA Tour this year after surgery to remove a golf ball-sized tumor from his brain, closed with a 68 to share medalist honors with Camilo Benedetti at 13-under 275.
Demsey was 197th on the money list this year, requiring him to return to the second stage.
Among those to advance at Southern Hills Plantation were former PGA Tour winners Robert Gamez, John Huston, Garrett Willis and Michael Bradley.
The 28-year-old Compton had his first heart transplant at age 12, but had a heart attack last October. He had another transplant in May, and recovered quickly enough to make it through the first stage by closing with a 68 to advance on the number.
He successfully petitioned the PGA Tour to ride a cart.
Had he made it through the second stage, Compton would have been assured at least temporary status on the Nationwide Tour. Now he will only be able to play on sponsor exemptions. He received one last week at Disney, where he made the cut and tied for 60th.
PGA Tour spokesman Ty Votaw said Compton was given six months to ride in a cart until he gets his full strength back.
In other qualifiers Saturday:
Riley, who played in the 2004 Ryder Cup, closed with a 69 to post all four rounds in the 60s. Also advancing were Ryder Cup assistant captain Olin Browne, former Presidents Cup player Carlos Franco of Paraguay and former tour winner Chris Smith.
Among those who did not finish among the top 20 were Billy Andrade and Len Mattiace, who lost a playoff in the 2003 Masters.
Among those who failed were Dicky Pride, former Ryder Cup player Per-Ulrik Johansson and television analyst Bobby Clampett.
The final stage of Q-school will be Dec. 3-8 at PGA West in La Quinta, Calif.