Since a few years, the laparoscopic sleeve gastrectomy (SG) has become the most performed bariatric operation worldwide. However, as with all bariatric procedures, SG also leads to vitamin and mineral deficiencies post-operatively and standard multivitamin supplements are probably not sufficient.The present study evaluates the effectiveness of a specialized multivitamin supplement for SG patients (WLS Optimum 1.0, FitForMe, Rotterdam, the Netherlands), compared to a standard multivitamin supplement (sMVS).A double-blind randomized controlled trial was performed. For 12 months, patients in the intervention group received WLS Optimum, containing elevated doses of multiple vitamins and minerals. Patients in the control group were provided with sMVS, containing 100% of the recommended dietary allowance.In total, 139 patients were available for analysis (WLS Optimum, n = 69; sMVS, n = 70). Intention-to-treat analyses revealed more folic acid deficiencies and higher serum vitamin B1 levels in the WLS Optimum group. Per protocol analyses showed that in patients using WLS Optimum, serum folic acid and vitamin B1 levels were higher, serum PTH levels were lower, and only one patient (2.6%) was anemic compared to 11 patients (17.5%) using a sMVS (p < 0.05 for all). No differences were found in prevalence of deficiencies for iron, vitamin B12, vitamin D, and other vitamins and minerals.This optimized multivitamin supplement only affected serum levels of folic acid, PTH and vitamin B1, and anemia rates compared to a sMVS. There is a clear need to further optimize multivitamin supplementation for SG patients. Besides, non-compliance with multivitamin supplements remains an important issue that should be dealt with.The study protocol was registered at the clinical trials registry of the National Institutes of Health (ClinicalTrials.gov; identifier NCT01609387).