Obstructive sleep apnea (OSA) and hypertension are independent risk factors of cardiovascular morbidities. This study aims to investigate the relationship between OSA, blood pressure (BP) control, and myocardial injury in patients with difficult-to-control hypertension. Patients with hypertension who required three or more medications were prospectively recruited at a tertiary referral center. In-laboratory polysomnography, followed by blood tests for fasting glucose, glycated hemoglobin, lipids, high-sensitivity troponin I (hsTnI), B-type natriuretic peptide (BNP), C-reactive protein, and advanced oxidation protein products were performed. After polysomnography, 24-hour ambulatory BP monitoring was arranged. A total of 98 participants were analyzed, with mean age 51 ± 9 years and body mass index 30 ± 5 kg/m2. Previously undiagnosed severe OSA (apneahypopnea index [AHI] ≥ 30 events/h) was present in 51 patients (52%). hsTnI was negatively correlated with nocturnal dip in systolic BP (r = -.205, P = .048). After controlling for confounders, including BP control, AHI and oxygen desaturation index (ODI) were positively correlated with hsTnI (r = .282, P = .009 and r = .279, P = .010, respectively) and C-reactive protein (r = .302, P = .005 and r = .285, P = .008, respectively), but not with BNP or advanced oxidation protein products. Age, ODI, and loss of nocturnal systolic BP dip were significant determinants of hsTnI level (β = .225, P = .022; β = .293, P = .003; and β = -.215, P = .029; R2 = .151). Age, female sex, 24-hour mean diastolic BP, and metabolic syndrome, but not indices of apnea severity, were predictors of BNP level. Unrecognized severe OSA was common in patients with difficult-to-control hypertension, and OSA severity was associated with myocardial injury, independent of BP control with medications. Registry: ClinicalTrials.gov, Title: A Cross-sectional Study of the Occurrence and Effect of Obstructive Sleep Apnea in Subjects With Resistant Hypertension, Identifier: NCT00843583, URL: https://clinicaltrials.gov/ct2/show/NCT00843583.