This study evaluated the effect of prasugrel alone, and in combination with low and high dose aspirin, on urinary metabolites of thromboxane A2 (TXA2) and prostaglandin I2 (PGI2), TX-M and PGI-M, respectively. 9 healthy males, aged 18–40, were enrolled in the 21-day study. Prasugrel was loaded at 60 mg on day 1 and maintained at 10 mg once daily until day 21. At day 8 aspirin 75 mg o.d. was introduced and the dose increased to 300 mg o.d. on day 15. On days 0, 7, 14 and 21 urine samples were obtained and TX-M and PGI-M assayed by mass spectrometry. Platelet aggregation to a TXA2-mimetic (U46619) was also determined at each time point. Data are presented as ng of urinary metabolite per mg creatine (mean±SEM). Data were analysed by one-way ANOVA with Bonferroni's post-test. Prasugrel alone did not reduce either TX-M (day 7, 0.24±0.02 ng per mg creatine; day 0, 0.28±0.04) or PGI-M (day 7, 0.15±0.03; day 0, 0.15±0.04), although both metabolites were reduced by the addition of low dose aspirin (day 14: TX-M, 0.09±0.01; PGI-M, 0.07±0.01; p<0.01 vs day 0). There were no further effects with the higher aspirin dose (p>0.05). Platelet aggregation to U46619 was largely inhibited by prasugrel, with no further effect of aspirin. Prasugrel alone preserves urinary PGI2 metabolites while inhibiting TXA2-driven platelet aggregation. Addition of aspirin reduces the excreted levels of metabolites of both TXA2 and vasoprotective PGI2.