Background: The prehospital emergency system is the first initiator of medical care as an alternative to hospitals and health care services that helps patients and injured people in critical situations and accidents. This study aimed to evaluate the cost-effectiveness of air ambulance versus ground ambulance regarding the patient's transportation and treatment. Methods: In this cost-effectiveness analysis study, 300 patients who were transferred to the Shohadaye HaftomTir hospital by air ambulance and 300 patients transferred by ground ambulance during the study period were selected in 2021-2022. This study examined the costs from the society's perspective. After drawing the decision tree model in TreeAge software, the incremental cost-effectiveness ratio was calculated; and to evaluate the strength of the analysis results, one-way and two-way sensitivity analyses were done on all costs and consequence parameters. Results: The effectiveness rate in the ground ambulance group and in the air ambulance group was 0.42591 and 0.5566, respectively, and the total cost of transportation and treatment by ambulance in these patients was $412.88 and for patients transported and treated by air ambulance was $11898.05. Therefore, air ambulance costs more and is more effective than ground ambulance, and the amount of incremental cost and effectiveness of air ambulance compared with ground ambulance was $11485.17 and 0.130773 units, respectively. The incremental cost-effectiveness ratio (ICER) of the 2 strategies was 87825.28, and the cost-effectiveness threshold was $7200. To determine the strength of the study results, one-way and two-way sensitivity analyses were done and the results of the cost-effectiveness analysis was not changed. Conclusion: Our study showed that ground ambulance is more cost-effective than air ambulance and the most important reason is that the total cost of air ambulance is 26 times more than ground ambulance, however, it is more effective than ground ambulance.