Weight and lipids are critical components of the metabolic syndrome, diabetes and cardiovascular disease. Past reviews considering weight loss on lipid profiles have been for ≤1 year follow-up and/or were for very overweight, obese or morbidly obese participants. This systematic review includes lifestyle interventions for adults (18-65 years), with a mean baseline BMI< 35 kg/m(2) , with weight and lipid differences over 2 years. Between 1990 and 2010, 14 studies were identified. Mean differences for weight and lipids were modest. However, weight loss at 2-3 years follow-up, produced significant beneficial lipid profile changes. These were similar to previous reviews conducted on heavier target groups and/or over shorter follow-up periods; cholesterol (1.3% decrease per kg lost) and triglycerides (1.6% fall per kg). Weight loss sustained longer than 3 years was not associated with beneficial lipid changes, suggesting that other lifestyle changes not just weight loss needs maintaining. Evidence linking lifestyle induced sustained weight loss with lipid profile changes in the long-term for this group is limited. Probable within-group differences (treatment vs prevention), would make further group separation prudent. Individual patient data analysis would facilitate this, uncover baseline, medication and confounding effects, and may identify successful program components enabling more effective obesity prevention and treatment strategies.