Changes in body weight (BW), risk factors and comorbidities 5 years after Roux‐en‐Y gastric bypass (RYGB) or different lifestyle interventions are compared. A total of 209 (75% women) severe obese adults were non‐randomly allocated to: (A) RYGB (n = 58), (B) weight loss (WL) camp (n = 30), (C) residential intermittent programme (n = 64) or (D) hospital outpatient programme (n = 57). Body weight, risk factors and comorbidities were assessed at baseline, 1 and 5 years. A total of 89 and 54% completed the 1‐ and 5‐year follow‐up. The RYGB group experienced more WL at 5 years (−23.9%, 95% CI [−27.7, −20.0]) compared with lifestyle groups: (B) (−9.2%, 95% CI [−16.9, −1.5]), (C) (−4.1%, 95% CI [−8.0, −0.1]) and (D) (−4.1 kg, 95% CI [−10.0, 1.8]) (all P < 0.001). No differences were observed between lifestyle groups, although groups B and C had significant WL after 5 years (all P < 0.05). Plasma glucose and high‐density lipoprotein cholesterol were improved in the RYGB group at 5 years compared with lifestyle groups (all P < 0.05). More patients in the RYGB group experienced remission of hypertension (P < 0.05). RYGB was associated with a lower BW, improved blood parameters and hypertension remission compared with lifestyle interventions at 5 years. However, significant WL was also achieved with lifestyle interventions.