Shad Edward Nichols was convicted in December 2002 of culpable negligent manslaughter in Simpson County Circuit Court.
The Mississippi Court of Appeals Tuesday upheld the conviction and sentence.
Nichols was convicted of fatally injecting Jennifer May with the painkiller at his home on November 28, 2000.
Prosecutors say Nichols kept OxyContin, a potent pain killer developed for cancer patients, at his trailer in Mendenhall.
Prosecutors say Nichols had the prescription filled in Scott County, returned home and gave the pills to the decedent and to two other teenagers. Prosecutors said May shot up twice with the drugs.
May was a 10th grader at Mendenhall High School.
The Appeals Court rejected all of Nichols' arguments on appeal.