Energy-efficient air cooling systems are always in demand. Direct evaporative coolers are energy-saving and have low cost, but in hot and humid areas, they produce an almost uncomfortable environment. Alternatively, modified indirect evaporative coolers with different technical configurations can produce better thermal output. This paper presents a simple thermodynamic approach developed to analyze, for comparison, the behavior of conventional and regenerative indirect evaporative coolers that comprise different process structures. The analysis is based on the energy balance of the coolers to consider which is more applicable for further modification. Similar performance cross-flow heat exchangers with separate air washers are adopted for both units. The two coolers are subjected to the same general summer operating conditions. The results showed that the conventional indirect evaporative cooler provided better cooling performance in terms of all thermal comparison parameters. The supply temperature trend in regenerative indirect evaporative cooler (RIEC) is higher by 23.4–34.1%, while its effectiveness is lower by 26–56% compared to that of the conventional indirect evaporative cooler (CIEC). The cooling capacity of CIEC is always higher at any air ratio value. At an equal secondary air flowrate where the primary air flowrate of RIEC is 25% more than that of CIEC, CIEC still generates lower air supply temperature and its effectiveness is higher. Thus, CIEC deserves priority attention for further development and additional improvement of performance.