This paper is based on a quality of life index study comparing 39 districts in Istanbul. The study is the third of a series of studies, where the first study was conducted and published in 2011 and the second in 2016. The results of the periodic research reveal the transformation of districts in Istanbul in terms of quality of life. The study, carried out on the same methods and parameters, aims to monitor the quality of life at the district level in Istanbul over the years. The weighted average method was used in the analysis made with the district-level 2020 data in Istanbul. According to the index results, Kadıköy, Beşiktaş, Bakırköy, Üsküdar, and Şişli are the districts with the highest quality of life, while Gaziosmanpaşa, Esenler, Sultanbeyli, Sultangazi, and Arnavutköy districts are in the last place. As a result of the clustering study, when evaluated in terms of 5 clusters, it is observed that 4.8 percent of the population of Istanbul lives in the first level, which is the highest quality of life, while 15.9% are second, 31.5% are third, 36.2% are fourth, and 11.6% are in districts with a fifth level of quality of life.