The causes of sudden sensorineural hearing loss (SSNHL) are unclear, and the condition cannot be treated with specific regimens. The present study was designed to explore the effects of alprostadil combined with hyperbaric oxygen (HBO) on hearing recovery and hemorheology in patients with SSNHL, and to analyze factors influencing treatment efficacy. in total, 104 patients with SSNHL were enrolled between January 2015 and July 2018 in a randomized controlled trial. Group A (n=52) received alprostadil treatment and Group B (n=52) were treated with HBO plus alprostadil. Following treatment, the overall recovery rates of tinnitus, aural fullness and vertigo in Group B were significantly higher than those in Group A (P<0.05). Low-, middle-and high-shear whole blood viscosity and whole blood viscosity in the two groups significantly decreased, and those in Group B were significantly lower than those in Group A (P<0.05). The present results indicated that the combination of alprostadil with HBO can improve the therapeutic effect on SSNHL, reduce blood viscosity and improve coagulation function, thus significantly promoting hearing recovery. Further, SSNHL treatment efficacy was influenced by age, time of onset, hearing threshold, presence or absence of tinnitus, plasma viscosity and serum C-reactive protein levels. The trial registration number for the present study was: NCT02563872.