INTRODUCTION:: Omega-3 fatty acid (n3 FA) consumption is associated with improved insulin sensitivity in some diabetic populations, but can cause adverse effects at high doses. The objective was to evaluate the tolerability of high-dose n3 FA supplementation in obstetric patients with diet-controlled gestational diabetes (GDM). METHODS:: Women with diet-controlled GDM between 24 and 30 weeks of gestation were randomized in a prospective, double-blind fashion to receive either 2200 mg daily of commercial fish oil (1300 mg eicosapentaenoic acid (EPA) + 900 mg docosahexaenoic acid (DHA)) or an identical placebo for a minimum of 6 weeks. Pre-and post-treatment evaluations were calculated using the homeostatic model assessment of insulin resistance (HOMA-IR) and measures of safety and tolerability. RESULTS:: In this pilot study, 14 GDM patients were randomized to treatment with fish oil (N=7) or placebo (N=7). Of these, 35.7% (3 in the treatment group, 2 in the placebo group) did not complete the treatment course due to intolerance. No clinically significant adverse effects, obstetric or neonatal complications were noted. Two patients in each group required initiation of medical therapy for glucose control subsequent to enrollment. While the pilot study was not adequately powered to detect a difference in objective measures of glucose control between the groups, no significant differences in fasting glucose, fasting insulin, or HOMA-IR levels were noted. CONCLUSION:: High dose omega-3 fatty acid supplementation appears to be safe in pregnancy, but some patients have bothersome side effects that may limit compliance. The use of omega-3 fatty acids to mitigate insulin resistance in gestational diabetes warrants further investigation.