BACKGROUND Vancomycin and teicoplanin are both antibiotics that have significant antimicrobial effects on Gram-positive cocci. AIM To explore the value of teicoplanin combined with conventional (vancomycin only) anti-infective therapy for the treatment of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis pulmonary infections. METHODS A total of 86 patients with methicillin-resistant Staphylococcus aureus or methicillin-resistant Staphylococcus epidermidis pulmonary infections, treated in our hospital between January 2018 and February 2020, were assigned to the study and control groups using a random number table method, with 43 patients in each group. The control group received conventional treatment (vancomycin), and the study group received both teicoplanin and conventional treatment. The following indicators were assessed in both groups: the time required for symptom relief, treatment effectiveness, serum levels of inflammatory factors (procalcitonin, interleukin-1 beta, tumor necrosis factor-alpha, C-reactive protein), clinical pulmonary infection scores before and after treatment, and the incidence of adverse reactions. RESULTS Patients in the study group were observed to have faster cough and expectoration resolution, white blood cell count normalization, body temperature normalization, and rales disappearance than patients in the control group (all P < 0.05); the total rate of effectiveness was 93.02% in the study group, higher than the 76.74% in the control group (P < 0.05). The pre-treatment serum levels of procalcitonin, interleukin-1 beta, tumor necrosis factor-alpha, and C-reactive protein as well as the clinical pulmonary infection scores were similar among the patients in both groups. However, the post-treatment serum levels of procalcitonin, interleukin-1 beta, tumor necrosis factor-alpha, and C-reactive protein as well as the clinical pulmonary infection scores were significantly lower in the study group than in the control group (P < 0.05). There was no significant difference in the incidence of adverse reactions between the groups. CONCLUSION Compared with conventional (vancomycin only) therapy, teicoplanin and vancomycin combination therapy for patients with pulmonary methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis infections can improve patient clinical symptoms, modulate serum inflammatory factor levels, and improve treatment efficacy, without increasing the risk of adverse reactions.