Acute low-frequency hearing loss (ALHL) is typically treated with combination therapy, including steroids and diuretics. To avoid unnecessary use of steroids we proposed a method of sequential administration using these two drugs, and compared the efficacy of our protocol with that of existing combination treatments. A prospective, randomized, open-label, single-blind, noninferiority clinical trial was conducted to investigate whether the effectiveness of sequential treatment is noninferior to that of combination treatment for ALHL. Ninety-two patients with ALHL received either steroids and diuretics simultaneously for 2 weeks (combination group), or diuretics for 2 weeks followed by steroids for another 2 weeks if they did not respond to diuretic treatment (sequential group). The primary outcome measure was a change in mean hearing threshold at three frequencies (125, 250, and 500 Hz) at 4 weeks after treatment. The mean hearing threshold of the low frequencies improved 20.0 and 17.2 dB in the combination and the sequential group, respectively. The 95% lower confidence interval was -8.0 dB and noninferiority was established at p < 0.05. At 4 weeks after treatment, the complete recovery rate was 80.5 and 82.9% in the combination and sequential groups, respectively. This is the first study on ALHL treatment following the establishment of Consolidated Standards of Reporting Trials (CONSORT). The sequential treatment is not inferior to combination treatment for ALHL, and therefore may be a better treatment guideline for ALHL considering that patients receive less steroid exposure and smaller restrictions in diuretic use compared with steroids.