In this non-randomized clinical pragmatic trial, we aimed to compare the effectiveness of an outpatient intensive lifestyle intervention (ILI) programme conducted in a tertiary care obesity rehabilitation centre with an outpatient moderate lifestyle intervention (MLI) programme at a secondary care obesity centre. Effectiveness was measured in terms of the 1-year effect each programme had on body weight, physical activity and health-related quality of life (HRQL). A total of 232 morbidly obese subjects were recruited to the ILI group and 140 to the MLI group, with retention rates of 78% and 44%, respectively. The ILI group had a significantly larger mean (95% confidence interval [CI]) weight loss than the MLI group, 11% (9%, 12%) vs. 2% (1%, 6%), P < 0.001, and a larger proportion of completers attaining ≥5% weight loss (71% vs. 33%), P < 0.001. Compared with the MLI group, the ILI group achieved a significant larger mean (95% CI) increase in the physical dimension of HRQL 6.9 (4.4, 9.3), P < 0.001, the mental dimension of HRQL 4.4 (1.4, 7.4), P = 0.018 and in the emotional dimension of HRQL 17.8 (12.8, 22.6), P < 0.001. There were no significant differences in terms of changes in physical activity. Compared with MLI, ILI was associated with significantly larger weight loss and better HRQL.