Potato is an important food and cash crop in Ethiopia which serves as a food security crop due to its nutritive value per unit area, wider adaptability and early maturity. However, the yield of the crop is constrained by a number of factors. Among the constraints use of inappropriate seed tuber size and limited availability of improved varieties are important limiting factors. Therefore, a field experiment was conducted during the 2019 irrigation season in Farta district 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 production of potato varieties in Farta district. The treatments consisted of four potato varieties (Belete, Shonkolla, Gudanie and Local (Key Dinch)) and three seed tuber sizes (small (25-38 g), medium (39-75 g) and large (>75 g)). The experiment was laid out in a Randomized Complete Block Design with three replications in factorial arrangement. Data collected on phenological, growth and yield related parameters were analyzed using SAS (Version 9.2) software. The results showed that, varieties and seed tuber size in their main effects significantly influenced days to 50% emergence, days to 50% flowering, main stem number per plant, yield of very small, small and medium sized tubers, unmarketable and total tuber yields. Tuber size and varieties interact to influence days to 90% maturity, plant height, large sized tuber yield and marketable tuber yields. The highest marketable tuber yield (39.13 t h-1) was recorded from large tuber sizes of Belete variety while the lowest marketable tuber yield (12.12 t h-1) was obtained from local variety which was planted using smaller seed tuber size. Based on the partial budget analysis, the use of large sized seed tubers for Gudanie variety gave the maximum net benefit (131,376.50 Birr ha-1). However, the use of small sized seed tubers for Belete variety gave the highest marginal rate of returns (1,657.14%). Based on the results of the present study, use of small sized seed tubers of Belete and Shonkolla varieties and medium sized seed tubers of Gudanie variety can be recommended for production of ware potato in the study site and areas with similar agro-ecologies. As the results are limited to one season and location, further study over more seasons and locations both during the off and rainy periods is required to establish the forceful recommendations. Keywords: Growth parameters, seed tuber size, tuber yield, variety, yield related parameters