BACKGROUND: Saline-filled intragastric balloons (IB) may be inserted for 6 months to promote weight loss. We aimed to assess potential benefits of repeating IB therapy. METHODS: One hundred eighteen consecutive subjects (median body mass index, 34.0 kg/m(2); interquartile range [IQR], 31.2-36.9) treated with IB were included in a prospective non-randomized multicenter study. RESULTS: Nineteen (16%) subjects had repeat IB therapy at their own request, either to prolong first treatment (n = 8) or after a IB-free interval (n = 11). Higher weight loss 3 months after first IB insertion independently predicted repeat therapy (P = 0.008). Median weight loss in subjects who had repeat therapy was lower with second vs first IB (9.0 vs 14.6 kg; 30.4% vs 49.3% excess weight [EW]; P = 0.003). Compared to subjects with single treatment (n = 99), those with repeat treatment (n = 19) had greater weight loss at first IB extraction (14.6 vs 11.0 kg; 49.3% vs 30.7% EW; P = 0.026) and 1 year later (12.0 vs 6.0 kg; 40.9% vs 20.8% EW; P = 0.008) but the difference became less than 2 kg starting at 3 years. At final follow-up (4.9 years; IQR, 3.4-6.7), the whole subject population had lost a median of 2.0 kg (IQR, -3.0 to 10.3) or 6.2% EW (IQR, -8.1 to 31.6) and identical proportions of subjects with single/repeat treatment had ≥ 10% baseline weight loss (26%) or bariatric surgery (32%). CONCLUSION: Higher weight loss at 3 months independently predicted repeat IB therapy; weight loss with the second IB was lower compared to first IB. Repeat treatment had no effect on proportions of subjects with ≥ 10% baseline weight loss or bariatric surgery at final follow-up.