Background: There is uncertainty regarding the efficacy of increasing n-3 long-chain PUFA (LCPUFA) intake during pregnancy in reducing the risk of gestational diabetes mellitus (GDM) and preeclampsia. Objectives: The objective was to determine whether n-3 LCPUFA supplementation in pregnancy reduces the incidence of GDM or preeclampsia. A secondary objective was to assess the effect of n-3 LCPUFA supplementation on perinatal complications. Design: This was a double-blind, multicenter randomized control trial - the DHA to Optimize Mother Infant Outcome (DOMInO) trial. Pregnant women (n = 2399) of <21 wk gestation were randomly assigned to receive DHA-enriched fish oil (800 mg/d) or vegetable oil capsules without DHA from trial entry to birth. The presence of GDM or preeclampsia was assessed through a blinded audit of medical records. Birth outcomes and prenatal complications were also assessed. Results: The overall incidences of GDM and preeclampsia were 8% and 5%, respectively, based on clinical diagnosis. The RR of GDM was 0.97 (95% CI: 0.74, 1.27) and of preeclampsia was 0.87 (95% CI: 0.60, 1.25), and they did not differ significantly between the groups. Birth weight, length, and head circumference z scores also did not differ between the groups. There were 12 perinatal deaths and 5 neonatal convulsions in the control group compared with 3 perinatal deaths and no neonatal convulsions in the DHA group (P = 0.03 in both cases). Conclusion: DHA supplementation of 800 mg/d in the second half of pregnancy does not reduce the risk of GDM or preeclampsia.Whether supplementation reduces the risk of perinatal death and neonatal convulsions requires further investigation. The DOMInO trial was registered with the Australian New Zealand Clinical Trials Registry as TRN12605000569606.