The beneficial effect of intentional weight loss on mortality is controversial. The purpose of this study was to conduct a systematic review and analyze the quality of prospective studies that assess weight loss on mortality. An electronic search at MEDLINE/PubMed, SciELO, and EBSCO data base, of studies with a follow-up of five or more years, published from January, 2000 to October, 2009, was conducted. Quality of the studies was assessed by Simonsen's criteria. Twenty studies were analyzed. At the beginning of the studies, the age of the subjects ranged from 20 to 101 years. Nine studies included those who intended to loose weight. The quality of the studies ranged from 8 to 17 points (out of 20). Weight loss increased the mortality rate in 15 studies and decreased it in 5. Seven of the studies assessing intention to loose weight showed that weight loss increased the mortality rate, whereas in two the mortality rate decreased. In three out of the four studies that assessed weight fluctuation, the mortality rate increased. These results underline the importance of preventing weight increase, as well as the need to avoid gaining or loosing weight more than 4%.