ABSTRACT Introduction Despite extensive efforts to identify effective treatments for COVID‐19, preventive strategies remain essential. Bromhexine hydrochloride (BRH), an over‐the‐counter mucolytic with potential TMPRSS2 inhibition, may reduce viral entry and thus serve as a prophylactic agent. Methods A retrospective questionnaire‐based study included 125 individuals reporting prophylactic BRH use. Demographic and clinical data were collected. COVID‐19 infection rates before and after BRH use were compared. Subgroup analyses were performed by vaccination status, prior infection, and duration of prophylaxis. Results Participants had a mean age of 56.5 years and a mean BMI of 25.6; 20% were vaccinated. Prior to BRH use, 62.4% reported COVID‐19 infection, compared to 11.2% after prophylaxis ( p < 0.0001). Significant reductions were observed in both vaccinated (48.1% vs. 3.7%, p = 0.002) and unvaccinated individuals (66.3% vs. 13.3%, p < 0.0001). Prior infection did not significantly influence outcomes ( p = 0.9248). Longer BRH use was associated with lower reinfection rates, decreasing from 33.3% (≤ 10 days) to 2.6% (≥ 30 days) ( p = 0.003). Conclusions BRH prophylaxis was associated with reduced reported COVID‐19 infection rates, independent of vaccination or prior infection, with greater benefit observed with longer use. Prospective controlled studies are required to confirm these findings.