Oxycodone is an opioid analgesic metabolized to oxymorphone and noroxycodone by cytochrome P450 (CYP) 2D6 and 3A4/5, respectively. This was a retrospective study to evaluate sex, age, urinary pH and concurrent medication use on oxycodone, oxymorphone and noroxycodone distributions. Urine specimens obtained from patients on chronic opioid therapy were analyzed by LC-MS-MS. There were 108,923 specimens from a subject's first or single visit, who were at least 18 years of age, and had documented physician-reported oxycodone use. The majority of specimens had detectable oxycodone urine concentrations (n = 106,852) resulting in oxycodone mole fractions (arithmetic mean ± SD) of 0.44 ± 0.27. Ninety-eight percent (n = 106,229) and 49% (n = 53,394) had detectable oxymorphone and noroxycodone, respectively. Oxycodone and oxymorphone mole fractions were lower in women compared with men (P < 0.0001). Mean ± SD age was 49.1 ± 12.9 years. Noroxycodone mole fractions were highest in the 65 years and older age group. Concurrent use of a CYP2D6 inhibitor, but not a CYP3A4/5 inhibitor, altered oxycodone and oxymorphone mole fractions. Dual inhibition of CYP2D6 and CYP3A4/5 did not result in a statistical difference upon comparison with CYP2D6 inhibitor or CYP3A4/5 inhibitor use. Patient factors affect oxycodone and metabolite mole fractions and suggest increased awareness of each contribution when attempting to monitor therapy with urine drug testing.