Obesity is a major public health issue in the United States. Many commercial weight loss programs are available, but their costs prohibit some people from participating. This study evaluated the effectiveness of Take Off Pounds Sensibly (TOPS), a low-cost, nonprofit weight loss program. Longitudinal mixed-effects repeated-measures modeling of the TOPS national database was used to model changes in weight for TOPS participants who joined in 2005, 2006, and 2007 and had at least one annual renewal between 2006 and 2008. Separate analyses were performed on individuals with consecutive annual renewal and those with nonconsecutive annual renewal. During the study period, 42,481 individuals renewed their membership at least once, including 2,427 individuals with nonconsecutive renewals. Individuals with consecutive renewals in TOPS lost 5.9–7.1% of their initial weight over a period of 1–3 years. People who remained in the program lost ∼6% of initial weight in the first year and maintained that weight loss for up to 3 years. TOPS participants with nonconsecutive renewal generally lost less weight than those with consecutive renewal. TOPS is associated with moderate weight loss among participants who remain in the program for at least 1 year. This degree of weight loss is likely to be clinically important for many individuals. TOPS is available at substantially lower cost than commercial weight loss programs, with similar results. Head-to-head trials of TOPS and popular commercial programs are needed.