Omega-3 fatty acids (n-3 FA) from oily fish are clinically useful for lowering triglycerides and reducing risk of heart attacks. Accordingly, patients at risk are often advised to take both aspirin and n-3 FA. However, both of these agents can increase bleeding times, and the extent to which the combination inhibits platelet function is unknown. The purpose of this pilot study was to determine the effects of a prescription omega-3 FA product (P-OM3) and aspirin, alone and in combination, on platelet aggregation assessed by whole blood impedance aggregometry (WBA). Ten healthy volunteers provided blood samples on four separate occasions: Day 1, baseline; Day 2, one day after taking aspirin (2 x 325 mg tablets); Day 29, after 28 days of P-OM3 (4 capsules/day); and Day 30, after one day of combined P-OM3 and aspirin. WBA was tested with two concentrations of collagen, with ADP and with a thrombin receptor activating peptide (TRAP). Compared to baseline, aspirin alone inhibited aggregation only with low-dose collagen stimulation; P-OM3 alone did not inhibit aggregation with any agonist; and combined therapy inhibited aggregation with all agonists but TRAP. Significant interactions between interventions were not observed in response to any agonist. In conclusion, P-OM3 alone did not inhibit platelet aggregation, but did (with two agonists) when combined with aspirin. Since previous studies have not reported a clinically significant risk for bleeding in subjects on combined therapy, P-OM3 may safely enhance the anti-platelet effect of aspirin.