Potato (Solanum tuberosum L.) is an important cash and food crop in Ethiopia. However, the yield of the crop is constrained by a number of factors. Among the constraints, the use of inappropriate seed tuber size and limited availability of improved varieties are the main ones. A field experiment was conducted to evaluate the effect of different tuber sizes on the growth and yield of potato varieties and to determine optimum seed tuber size for economical feasible production of potatoes during the rainy season at Sekela District in 2024. The experiment consisted of four potato varieties (Tesfa, Worku, Gera and Local) and three seed tuber sizes: small (25-38g), medium (39-75g) and large (>75g). The experiment was laid out in a Randomized Complete Block Design with three replications in factorial arrangement. The collected data on phenology, growth, yield and quality related parameters were analysed using SAS (Version 9.4) software. The results showed that varieties and seed tuber size significantly influenced days to 50% emergence, days to 50% flowering, stem number per plant, average tuber number per plant, unmarketable tuber yield, and dry matter content, tuber weight per plant. The interaction effect of seed tuber size and variety significantly influenced days to 90% maturity, large sized tuber yield, marketable tuber yield and total tuber yields. The highest marketable tuber yield of 37.26 t ha -1 was recorded from the large tuber sizes of Tesfa variety, while the lowest marketable tuber yield of 10.79 t ha -1 was obtained from a local variety with smaller seed tuber size but local variety matured earlier as compared to improved variety which is related to early emergence and flowering. Based on the partial budget analysis of the present study Tesfa with Large tuber size gave the highest net benefit of 1252630Birr ha with an acceptable level of MRR value of 173.66%; Tesfa with medium seed tuber size a good net benefit of 1,220,647Birr ha -1 and high acceptable level of MRR of 159.32%. However, since the study was conducted in one season and location, further study over seasons and locations is recommended in order to generate a more reliable and sustainable result. -1