Positive airway pressure (PAP) therapy adherence rates range from 30% to 60%, yet adherent patients may still express dissatisfaction with treatment. The identification of factors affecting PAP tolerance could provide insight into its impact on adherence. Patients with obstructive sleep apnea presenting for first follow-up visit after newly initiating PAP therapy were given a 10-question PAP tolerance survey encompassing domains of psychosocial perception, practical issues, and side effects, utilizing 10-point visual analog scales. Relationships between adherence data, tolerance scores, and patient variables (demographics, sleep-related factors, comorbidities, usage data) were explored via 2-tailed t tests, multivariable regression analysis, and recursive partitioning regression trees with a significance level of P ≤ .05. For 105 patients, tolerance scores were higher in patients considered adherent to therapy (P = .033), as were scores for individual survey questions addressing the ability to fall asleep (P = .013) and sleep through the night (P = .020). Depression positively (P = .006) and insomnia medication use negatively (P = .010) predicted tolerance score. Data-driven tolerance score cutoffs were identified to correlate with PAP adherence, with higher tolerance scores correlating with greater adherence rates. PAP tolerance may play an important role in therapy adherence. Tolerance can be statistically defined and categorized based on prior adherence data. Its utility as a predictive tool in assessing future adherence is warranted. Tekumalla S, Plawecki A, Kaffenberger T, etal. The relationship between positive airway pressure tolerance and adherence: defining a new metric. J Clin Sleep Med. 2024;20(7):1033-1038.