Objective To compare cerumenolytic effects of docusate sodium and of 2.5% sodium bicarbonate - In vitro study; observe characteristics of the solution, using ultraviolet–visible (UV/Vis) spectroscopy, and measurement of cholesterol levels. Methods Samples of human cerumen were mixed to form a relatively homogenous paste. Samples of about 500 mg were weighed and packed at the bottom of the test tubes. To each tube was added 1.5 ml of either docusate sodium or 2.5% sodium bicarbonate. Tubes were incubated at 36.4 °C in a water bath for 15, 30 or 60 min. Following incubation, the supernatant solution was pipetted into a cuvette. The cerumenolytic efficacy was defined as the absorbance (recorded at 350 nm and 400 nm) of the solutions. Results were the average of three replicates. A cholesterol level of each sample was then determined to confirm the result. Results Turbidity was much greater in tubes containing 2.5% sodium bicarbonate, indicating dissolution of cerumen. Mean difference of absorbance values measured at 350 nm and 400 nm after 15, 30, 60 min digestions were 1.93 [95%CI 1.49–2.38, p-value <0.001] and 1.81 [95%CI 1.21–2.41, p-value <0.001], respectively. Furthermore, levels of cholesterol were greater in tubes containing 2.5% sodium bicarbonate solution after digestion than in tubes containing docusate sodium; 11 mg/dl [95%CI 1.47–24.14, p-value = 0.083] Conclusion Both spectrophotometric and cholesterol level assessments suggest that 2.5% sodium bicarbonate has a higher cerumenolytic effect than docusate sodium. In other words, cerumen can be dissolved in 2.5% sodium bicarbonate much better than docusate sodium in a time-dependent manner.