Objective To explore the influence of ambroxol hydrochloride on oxygenation index, D-D and inflammatory indexes in elderly patients with pneumonia, and its predictive efficiency for prognosis of the patients . Methods A total of 226 elderly pneumonia patients admitted to the General Practice Department of Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 2022 to January 2023 were enrolled and randomly divided into a control group and an ambroxol hydrochloride group, with 113 cases in each group. After exclusion and grouping modification, 110 patients were eventually included in each of the two groups. According to the severity of the disease, the control group was assigned into severe and mild subgroups (36 and 74 cases, respectively), and the ambroxol hydrochloride group also into severe and mild subgroups (38 and 72 cases, respectively). The control group was given routine treatments such as oxygen inhalation support, sedation, cough relieving and phlegm relieving, while the ambroxol hydrochloride group was given intravenous injection of ambroxol hydrochloride on the basis of routine treatments. The effective rate, as well as oxygenation index, and D-D, C-reactive protein (CRP) and procalcitonin (PCT) levels before and after treatment were observed in the two groups. Receiver operating characteristic (ROC) curve was plotted to analyze the predictive performance of each indicator. Kaplan-Meier curve was drawn to analyze the survival of these patients. Results The total effective rate was significantly higher in the ambroxol hydrochloride group than the control group [89.09% (98/110) vs 70.91% (78/110); P<0.05]. When compared to the levels before treatment, the patients from the two mild subgroups of the control and ambroxol hydrochloride groups obtained significantly higher oxygenation index [(275.69±27.82) vs (153.26±11.89) mmHg, (297.19±23.53) vs (156.87±12.47) mmHg] and lower D-D level [(1.79±0.66) vs (2.43±0.91) mg/L, (1.34±0.47) vs (2.41±0.88) mg/L] after treatment; and those of the two severe subgroups had obviously increased oxygenation index [(257.58±25.19) vs (126.33±12.19) mmHg, (279.51±27.02) vs (127.83±13.53) mmHg] and decreased D-D level [(1.93±0.73) vs (2.56±0.78) mg/L, (1.77±0.59) vs (2.61±0.79) mg/L]. Ambroxol hydrochloride treatment resulted in statistically higher oxygenation index [(297.19±23.53) vs (275.69±27.82) mmHg, (279.51±27.02) vs (257.58±25.19) mmHg] and lower D-D level [(1.34±0.47) vs (1.79±0.66) mg/L, (1.77±0.59) vs (1.93±0.73) mg/L] in either mild or severe patients (P<0.05). Both routine and ambroxol hydrochloride treatment decreased CRP [(54.35±9.27) vs (87.55±8.19) mg/L, (41.56±9.57) vs (88.49±9.17) mg/L] and PCT [(0.99±0.37) vs (1.89±0.52) μg/L, (0.53±0.21) vs (1.90±0.49) μg/L] levels in the two mild subgroups, and the ambroxol hydrochloride group obtained more lower CRP [(41.56±9.57) vs (54.35±9.27) mg/L, (55.12±7.58) vs (60.58±9.82) mg/L] and PCT [(0.53±0.21) vs (0.99±0.37) μg/L, (0.75±0.25) vs (1.12±0.55) μg/L] levels in both mild and severe patients than the control group (all P<0.05). After the follow-up of 28 d, the cumulative survival rate was notably higher in the ambroxol hydrochloride group than the control group [89.09% (98/110) vs 69.09% (76/110), P<0.001]. The area under the ROC curve of oxygenation index, D-D level, combined with inflammatory markers CRP and PCT for prognosis of elderly pneumonia patients was 0.837, with a sensitivity of 88.50 and a specificity of 78.30. Conclusion Ambroxol hydrochloride can promote the treatment effectiveness in elderly pneumonia patients, significantly improving their oxygenation index, D-D level, inflammatory indicators, and survival rate. The combination of oxygenation index and D-D, CRP and PCT levels has high predictive value for patient prognosis, and can be further promoted and applied in clinical practice.