Objective To observe the short-term effect and safety of hyperbaric oxygen combined with edaravone and ozagrel sodium in treating progressive cerebral infarction. Methods A total of 65 in-patients with acute progressive cerebral infarction were randomly divided into two groups: 33 in-patients in the trial group were treated by hyperbaric oxygen combined with edaravone and ozagrel sodium, while the other 32 in-patients in the control group were treated by edaravone and ozagrel sodium. The course of treatment was 14 days. The following indications were assessed before and after the treatment respectively: the national institutes of health stroke scale (NIHSS), activities of daily living (ADL), and clinical effects. Results This study showed that the scores of both ADL and NIHSS in the trial group were higher than those in the control group, with significant differences (Plt;0.05). The clinical effective rate of the trial group was 90.91% which was obviously higher than the control group with a significant difference (P=0.028). There were no obvious adverse reactions in both groups. Conclusion Hyperbaric oxygen combined with both edaravone and ozagrel sodium is notable in short-term effect and safe, thus it is worth being popularized in clinical treatment.