Background: The prevalence of obstructive sleep apnea (OSA) is very high in stroke patients, whereas the acceptance of positive airway pressure (PAP) therapy is low. Although telemedicine offers new options to increase acceptance, effective concepts and patient groups are not yet known. Objective: The aim of this study was to investigate the effect of a telemedicine concept consisting of telemonitoring and support when usage time drops. Methods: PAP naive stroke patients with apnea-hypopnea index (AHI) >15 were randomized in a prospective parallel design comparing home therapy with standard care (SC) as opposed to telemedicine care (TC) over a period of 6 months. The TC group received a standardized phone call to offer help and advice if the average weekly usage of PAP fell below 4 h/night. Results: Eighty patients were included, 5 were lost to follow-up, 75 (20 females, age: 57.0 +/- 9.9, body mass index: 30.9 +/- 6.0 kg/m(2), AHI: 39.4 +/- 18.6) were evaluated. While inpatient usage was similar in both groups, a significant difference was identified after 6 months of receiving home therapy (TC: 4.4 +/- 2.5 h, SC: 2.1 +/- 2.2 h; p < 0.000063). On average, 4.7 +/- 3.1 interventional phone calls were needed (173 calls in total, ranging from 0 to 10 calls per patient), primarily for the purpose of motivation (61.3%), mask problems (16.2%), nasopharyngeal complaints or humidification issues (11.2%), and technical questions (10.6%). Sleepiness (Epworth Sleepiness Scale [ESS]) differed significantly (TC: 3.7 + 3.2, SC: 6.1 + 4.1; p = 0.008), as well as systolic blood pressure, which was available in a subgroup of 55 patients (TC: 129.5 + 15.2 mm Hg, SC: 138.8 + 16.1 mm Hg; p = 0.034). Conclusion: A concept of telemonitoring and short telephone calls from the sleep lab raised PAP therapy adherence significantly in a group of stroke patients with moderate to severe OSA.