Rationale: Characteristics associated with adherence to long-term oxygen therapy (LTOT) in COPD remain unclear. Objectives: To identify patient characteristics at the time of oxygen initiation associated with its adherence. Methods: We conducted a secondary analysis of data from 359 COPD participants assigned to oxygen in the Long-term Oxygen Treatment Trial. Participants were prescribed continuous (n = 214) or intermittent (n = 145) oxygen based on desaturation patterns at study entry. At the time of initial prescription, participants rated their perceived readiness, confidence, and importance to use oxygen on a 0–10 scale (0 = not at all, 10 = very much). During follow-up, they self-reported average hours per day of use (adherence). Adherence was averaged over short-term (0–30 days), medium-term (months 9–12), and long-term (month 13 to last follow-up) intervals. Multivariable logistic regression models explored characteristics associated with high adherence (≥16 h/day [continuous] or ≥8 h/day [intermittent]) during each time interval. Results: Participant readiness, confidence, and importance at the time of oxygen initiation were associated with high short- and medium-term adherence. For each unit increase in baseline readiness, the odds of high short-term adherence increased by 21% (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.05–1.40) and 94% (OR 1.94, 95% CI 1.45–2.59) in the continuous and intermittent groups, respectively. In both groups, high adherence in the medium-term was associated with high adherence in the long-term (continuous, OR 12.49, 95% CI 4.90–31.79; intermittent, OR 38.08, 95% CI 6.96–208.20). Conclusions: Readiness, confidence, and importance to use LTOT at initiation, and early high adherence, are significantly associated with long-term oxygen adherence.