Background: Chronic obstructive pulmonary disease (COPD) is characterized by the impact of bad air, often progressive and irreversible, caused by a combination of different lung diseases, damage to the lungs, and emphysema, followed by inhalation of bad air and gases, especially smoke, causes, and often affects lung disease with many differences. By adding lactoferrin along with N-acetylcysteine (NAC), it targets nuclear factor-κB (NF-κB), which is responsible for inflammatory responses. This combination of NAC 600 + lactoferrin 50 mg offers synergistic effects and reduces mucus hypersecretion (as a mucolytic agent). Objective: This study was a randomized, open-label, actively controlled, prospective, single-center, two-arm, parallel to assess the efficacy, safety, and tolerability of the combination of NAC 600 + lactoferrin 50 mg against NAC 600 mg in the symptomatic treatment of patients suffering from productive cough associated with acute bronchitis. Materials and methods: The study was conducted under a qualified investigator at a single center in India. To assess the primary efficacy of the investigational products, assessment through a modified cough and sputum relief questionnaire was evaluated at baseline days 0, 3, 5, and 8. Secondary efficacy was evaluated through a 7-point Likert scale, bronchial severity score (BSS), and global clinical impression of improvement or change (CGIC); secondary safety endpoints were measured through adverse events (AEs) or serious AEs (SAEs) collected during the study. Results: It was observed that the combination of NAC and lactoferrin showed better primary and secondary efficacy results with respect to the treatment of acute bronchitis. The rate of reduction in the severity of acute bronchitis and improvement of breathing condition/general well-being is also showing better results in combination products compared to NAC 600 mg. SAEs were not reported during the conduct of the study. Conclusion: Based on the study results/data, it can be concluded that the combination of NAC and Lactoferrin shows better efficacy results with no linked AEs with respect to the treatment of acute bronchitis compared to single treatment. However, long-term studies will be done to evaluate the long-term effectiveness of the combination of NAC and lactoferrin.