Objective: To optimize anti-coxsackie B complex capsule for treating myocarditis induced by coxsackie B virus with the method of orthogonal test. Method: The optimized prescription of anti-coxsackie B complex capsule was selected according to the survival time of mice after oxygen deficiency with the method of orthogonal t value design. The optimized prescription was verified by anti-stress reaction experiments including tolerance to oxygen deficiency after myocardial ischemia and weight loading swimming. Result: Four of the seven components in the original prescription were selected preferentially to compose the optimized prescription, including Panax quinquefolius, Astragalus mongholicus, Radix Ophiopogonis and Chinese magnoliavine fruit. Both the original prescription and the optimized prescription could remarkably prolong the survival time of oxygen deficient mice and the swimming time of weight loading mice, however, there was no significant difference between the two prescriptions. Conclusion: The optimized prescription had similar effects on elevating the ability of anti-stress action in mice as the original one with less dosage.