Background: Continuous positive airway pressure (CPAP) is considered as the standard therapy for obstructive sleep apnea syndrome (OSAS), but some patients with OSAS are unable to accept CPAP due to nasal obstruction and poor nasal airflow. Objectives: We assessed the influence of nasal resistance before beginning CPAP treatment on the initial acceptance of CPAP in OSAS patients. Methods: The study subjects comprised 77 patients (74 males, 3 females) with primary OSAS, all of whom received CPAP treatment with nasal masks. Before trials, all subjects underwent overnight polysomnography, and nasal resistance was measured with active anterior rhinomanometry in the seated position on the first day of CPAP trial. Results: The CPAP treatment was accepted by 56 patients after the initial trials with overnight polysomnography. Body mass index, the number of apnea/hypopnea episodes per hour (apnea/hypopnea index; AHI), and the number of episodes per hour with an oxygen desaturation of >3% (oxygen desaturation index) were significantly higher (p < 0.01) and nasal resistance was lower (p = 0.003) in patients who accepted CPAP than in those who did not. Logistic regression analysis, with patient age, body mass index, Epworth sleepiness scale score, AHI, oxygen desaturation index, and nasal resistance before CPAP treatment as explanatory variables, showed that nasal resistance (OR + 0.1 Pa/cm3/s: 1.48; p = 0.002) and AHI (OR + 1 event/h: 0.93; p = 0.003) were significant factors for CPAP non-acceptance. Conclusions: Nasal resistance before the beginning of CPAP treatment has a significant effect on the acceptance of CPAP in OSAS patients, and hence, could be a predictive parameter for the initial acceptance of CPAP.