Introduction: With increasing reports about Corynebacterium striatum, its potential pathogenicity and clinical significance are drawing more attention in recent years. Methodology: During a 14-month period, Corynebacterium striatum strains were routinely isolated in lower respiratory tract samples of the inpatients in a tertiary hospital in China, and the suspected isolates were identified with VITEK-2 ANC card and 16S rRNA sequencing technique, respectively. Pulsed-field gel electrophoresis (PFGE) was employed to discriminate different clones, and biofilm-producing abilities of different strains were compared. Results: A total of 82 strains of Corynebacterium striatum were mainly isolated from neurosurgery patients (45.1%, 37/82). Three epidemic clones (type D, F, and I) were identified, accounting for 82.9% (68/82) of strains. All 82 C. striatum strains were all sensitive to vancomycin, and resistant to ceftriaxone, imipenem, and ciprofloxacin. One week before C. striatum isolation, 89.0% (73/82) patients showed lower levels of hemoglobin, 93.9% (77/82) of patients received treatment of several kinds of antibiotics, and 41.5% (34/82) patients with glucocorticoid, and 46.3% (38/82) of patients showed disturbed consciousness at different levels. Conclusions: Corynebacterium striatum strains isolated during this study were mainly multidrug resistant, and the predominant clones could rapidly transmit among susceptible inpatients. Corynebacterium striatum seems to be an important pathogen for patients with specific risk factors, especially for the ones with lower hemoglobin levels who are being treated with broad-spectrum antibiotics.