Background: Hypertriglyceridaemia is a recognised metabolic abnormality in HIV-infected people, increasing in severity in people treated with highly active antiretroviral therapy (HAART). An alternative treatment for hypertriglyceridaemia in non-HIV-infected populations is omega-3 fatty acid supplementation. This study aimed to compare the effectiveness of omega-3 fatty acid supplementation and placebo in lowering fasting triglyceride levels in HIV-infected patients on HAART. Methods: A placebo-controlled, randomised, double-blind trial in participants on stable HAART with fasting triglycerides of >3.5 mm to 10.0 mm using 9 g of omega-3 fatty acids versus placebo (olive oil) after a 6-week lead in on dietary therapy. Results: Eleven patients were enrolled. The mean triglyceride level for the population decreased from 5.02 mm at baseline to 4.44 mm (–11.6%) after dietary intervention and 3.37 mm (–32.9%) after the 8-week treatment period. In the omega-3 fatty acid arm of the study, triglycerides fell from 5.34 mm to 5.02 mm (–6%) after dietary intervention and to 2.30 mm (–56.9%) after the treatment period. In the placebo arm of the study, triglycerides fell from 4.77 mm to 4.05 mm (–15.1%) after dietary intervention and to 4.08 mm (–14.5%) after the treatment period. Using the random effects model, a statistically significant effect on triglycerides of omega-3 fatty acid versus placebo was found (χ2 = 6.04, P = 0.0487). The estimated difference between groups for change in mean triglycerides over 8 weeks was –2.32 mm (95% CI –4.52, –0.12 mm). Conclusions: Omega-3 fatty acids are likely to be an effective treatment for hypertriglyceridaemia in HIV-infected males on HAART.