Objective To evaluate the clinical efficacy and safety of compound polymyxin B ointment combined with desonide cream for the treatment of subacute or chronic eczema. Methods A multicenter, randomized, double?blind, parallel?group, controlled clinical study was conducted. Totally, 144 patients with subacute eczema and 144 patients with chronic eczema were enrolled into this study, and both randomly and equally divided into the test group and control group. The test group and control group firstly topically applied compound polymyxin B ointment and its vehicle respectively, then both topically applied desonide cream 3 hours later. The drugs or vehicle were applied twice a day in all the patients. Patients′ symptoms and signs (including degree of itching, inflammation, erosion/exudation and infiltration/thickening, as well as area of target lesions) were evaluated, and the time to onset and duration of itching?alleviating effect were recorded. The clinical efficacy and safety of treatments were analyzed and compared between the test group and control group. Results The total symptom and sign scores significantly decreased to different extents on days 7 and 14 in the test group(subacute eczema patients:6.09 ± 2.78 and 3.68 ± 3.18 vs. 13.44 ± 1.66; chronic eczema patients: 6.56 ± 2.68 and 4.38 ± 3.27 vs. 12.96 ± 1.16)and control group(subacute eczema patients:8.26 ± 3.17 and 5.28 ± 4.05 vs. 13.60 ± 1.75;chronic eczema patients: 8.84 ± 2.90 and 6.25 ± 3.78 and vs. 12.64 ± 1.18)compared with those at baseline. Moreover, the total symptom and sign score of patients with subacute or chronic eczema was significantly lower in the test group than in the control group on days 7 and 14(all P<0.05). A significant increment was observed in the degree of decrease in scores for itch, infiltration/thickening in patients with subacute eczema in the test group compared with that in the control group(all P<0.01), as well as in scores for itch, infiltration/thickening and area of target lesions in patients with chronic eczema in the test group compared with those in the control group (all P < 0.05). In addition, patients with subacute eczema in the test group showed significantly shorter onset and longer duration of itching?alleviating effect than those in the control group(both P<0.05). The time to onset of itching?alleviating effect was also significantly shorter in patients with chronic eczema in the test group than in those in the control group(P<0.000 1), but there was no significant difference in the duration of it between the two groups of patients with chronic eczema. Clinicians and patients were both more satisfied with therapeutic effects in the test group than in the control group(all P<0.05). Conclusions Topical compound polymyxin B ointment can increase the efficacy of topical desonide cream for the treatment of subacute or chronic eczema, especially subacute eczema. Compound polymyxin B ointment also shows a favorable therapeutic effect on itching and infiltration/thickening in patients with eczema.