The aim of this study was to describe the long-term efficacy and safety of low-calorie diets (LCDs; providing 900 kcal day−1) in obese patients who have failed to achieve adequate weight loss with standard medical management and are non-eligible for surgical therapeutic options. Charts from a regional hospital-based outpatient bariatric programme were reviewed. Eight patients (75% male, age 60.1 ± 7.8 years) with severe obesity (body mass index 57.1 ± 8.8 kg m−2) and undergoing long-term LCD (33 ± 10 months) were identified. Variables of interest included anthropometric, cardiovascular risk and nutritional parameters, thyroid, renal and liver function, changes in medications, side effects and adverse events. Average weight loss was 44 ± 15 kg (27 ± 13% of initial weight) at 24 months. Long-term management with LCD resulted in substantial and sustained improvements in glucose homeostasis, blood pressure and lipid profile. LCD was well tolerated with minor self-limited side effects. Over the follow-up period, two subjects underwent coronary revascularization and one patient underwent knee replacement surgery – all recovered without complications. These findings suggest that in selected obese patients (non-eligible for surgery), long-term management with LCD may provide an alternative option for substantial and sustainable weight loss with significant improvements in metabolic and cardiovascular health.