Objectives: Evidence suggests that both N-Acetyl-L-cysteine (NAC) and NAC in combination with propolis (NAC-P) reduce symptoms of acute bronchitis and improve Health-Related Quality of Life (HRQoL). This study aimed to compare the impact of NAC and NAC-P therapy on acute bronchitis patients' quality of life. Design, setting, and subjects: A randomized, single-blind parallel-group study was achieved at Municipal Institute for Lung Diseases and Tuberculosis Medical Centre, Belgrade, Serbia. Patients with acute bronchitis were randomly assigned into two groups to receive NAC (200mg three times a day) or NAC-P (200mg+80mg three times a day) orally for a minimum of ten days. HRQoL of patients was measured twice (at two appointments) using the Leicester Cough Questionnaire (LCQ) and EQ-5D questionnaires. Results: The study included 42 patients in the NAC-P group and 43 in the NAC group. The correlation between the LCQ total score and Health State Values (HSV) was positive and statistically significant in the NAC-P and the NAC groups at the second appointment. The differences between values of EQ-5D scores were slightly higher (but not statistically significant) in the NAC-P group compared to the NAC group, indicating a more remarkable improvement of HRQoL using NAC-P. Conclusion: NAC-P and NAC may improve HRQoL in patients with acute bronchitis. EQ-5D scale values indicated that NAC-P might improve quality of life more than NAC. Our results may provide the basis for better decision-making by healthcare professionals when choosing the right therapy.