Objective To investigate the clinical value of multi-slice spiral CT (MSCT) combined with serum procalcitonin (PCT) level in guiding the use of antimicrobial agents in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD). Methods A total of 100 patients with acute exacerbation of COPD who were admitted to the hospital from February 2016 to February 2018 were selected as study subjects. They were divided into the control group and the observation group by the random number table method, with 50 cases in each group. The control group was treated with selected antimicrobial agents under the guidance of serum PCT level while the observation group was treated with selected antimicrobial agents under the guidance of MSCT combined with serum PCT level. Changes of laboratory indicators before and after treatment, course of treatment with antimicrobial agents, length of hospital stay, treatment cost, followup prognosis and drug safety were observed. Results There was no significant difference in WBC, CRP or PCT between the two groups before treatment (P>0.05). The WBC, CRP and PCT in both groups were significantly decreased after treatment, and they were significantly lower in the observation group than in the control group (P<0.05). The course of treatment with antimicrobial agents and length of hospital stay of the observation group were significantly shorter than those of the control group, and the treatment cost was significantly less than the control group(P<0.05). Conclusion MSCT combined with serum PCT level is of certain clinical guiding value in the use of antimicrobial agents in patients with acute exacerbation of COPD.