Transformer operation and maintenance methods have an influence on its operational reliability and maintenance cost, which can influence the life cycle cost further. Therefore, optimizing the operation and maintenance strategy is of great significance to reduce the life cycle cost. Based on the Weibull distribution failure probability model, the life efficiency index is proposed and established to quantitatively measure the effect of maintenance on the operating life of the transformer. The total life cycle cost of transformers from design, purchase, maintenance to decommissioning is analyzed. The average annual cost per life cycle is chosen as the objective function. Under the constraints of operational reliability, maintenance levels and life efficiency index, the cuckoo algorithm is used to optimize the maintenance time, maintenance level, and operating life parameters in the operation and maintenance strategy. Comparing to Particle Swarm Optimization (PSO) and Genetic Algorithm (GA), the results obtained by the cuckoo algorithm are better. Not only the annual average cost is less, but also life efficiency index is higher, which can provide certain guarantees for transformer operation and maintenance. This work is supported by National Natural Science Foundation of China (No. 2016YFB0101900) and Science and Technology Project of Jiangsu Electric Power Company (No. SGJSJX00SZJS1601616).