This study aimed to compare the antimicrobial activities of topical agents against Propionibacterium acnes isolated from patients admitted to a hospital in Shanghai, China. The minimal inhibitory concentrations of the cultured P. acnes were determined in accordance with the Clinical and Laboratory Standards Institute. Susceptibilities to clindamycin and erythromycin were compared in terms of gender, age, disease duration, previous treatment, and disease severity. A total of 69 P. acnes strains were isolated from 98 patients (70.41%). The susceptibility to triple antibiotic ointment (neomycin/bacitracin/polymyxin B) and bacitracin was 100%. The susceptibility to fusidic acid was 92.7%. The resistance rates to neomycin sulfate, erythromycin, and clindamycin were 11.7%, 49.3%, and 33.4%, respectively. The high resistance rate to clindamycin and erythromycin was significantly affected by gender, previous treatment, and disease severity rather than by age and disease duration. Topical antibiotics should not be used separately for long-term therapy to avoid multiresistance. The use of topical antibiotics should be determined by clinicians on the basis of clinical conditions.