Background Obstructive sleep apnea (OSA) contributes to the generation, recurrence, and perpetuation of atrial fibrillation, and it is associated with worse outcomes. Little is known about the economic impact of OSA therapy in atrial fibrillation. This retrospective cohort study assessed the impact of positive airway pressure (PAP) therapy adherence on health care resource use and costs in patients with OSA and atrial fibrillation. Methods and Results Insurance claims data for ≥1 year before sleep testing and 2 years after device setup were linked with objective PAP therapy use data. PAP adherence was defined from an extension of the US Medicare 90‐day definition. Inverse probability of treatment weighting was used to create covariate‐balanced PAP adherence groups to mitigate confounding. Of 5867 patients (32% women; mean age, 62.7 years), 41% were adherent, 38% were intermediate, and 21% were nonadherent. Mean±SD number of all‐cause emergency department visits (0.61±1.21 versus 0.77±1.55 [ P =0.023] versus 0.95±1.90 [ P <0.001]), all‐cause hospitalizations (0.19±0.69 versus 0.24±0.72 [ P =0.002] versus 0.34±1.16 [ P <0.001]), and cardiac‐related hospitalizations (0.06±0.26 versus 0.09±0.41 [ P =0.023] versus 0.10±0.44 [ P =0.004]) were significantly lower in adherent versus intermediate and nonadherent patients, as were all‐cause inpatient costs ($2200±$8054 versus $3274±$12 065 [ P =0.002] versus $4483±$16 499 [ P <0.001]). All‐cause emergency department costs were significantly lower in adherent and intermediate versus nonadherent patients ($499±$1229 and $563±$1292 versus $691±$1652 [ P <0.001 and P =0.002], respectively). Conclusions These data suggest clinical and economic benefits of PAP therapy in patients with concomitant OSA and atrial fibrillation. This supports the value of diagnosing and managing OSA and highlights the need for strategies to enhance PAP adherence in this population.