Abstract: Potato yields in developing countries are below potential yield because potato production is mainly constrained by lack of quality seed. Lack of potato seed systems to provide farmers with quality clean and certified potato seed has led majority of farmers save their own seed. Such potato seed is characterized by systemic viral and bacterial diseases that are transmitted from generation to generation and this leads to low crop yields. The study was aimed at exploring the use of tissue culture and aeroponics techniques in the production of quality potato seed. Potato plantlets were produced in the tissue culture laboratory at Bvumbwe Research Station, 15? 41' 0" South, 35? 8' 0" East in Thyolo district of Malawi and then transferred to an aeroponics facility at Njuli Estate, 15? 41' 0" South, 35? 8' 0" East in Chiradzulu district of Malawi. The four potato genotypes did not differ on plant growth performance, but responded differently to aeroponics system in terms of mini tuber yield and stolon numbers. Genotypes CIP381381.20 and CIP381381.13 showed superiority among the other tested genotypes in terms of tuber number per plant. Genotype CIP381381.20 produced significantly higher number of stolons than the rest. In this study, on an average 30 tubers were produced per plant under aeroponics system which is six times more than the conventional (use of soil-based substrate) seed potato production system under screen house conditions (5 tubers per plant) under Malawian conditions.