We updated the 2002 Antiplatelet Trialists’ Collaboration meta-analysis of antiplatelet therapy to assess the effects of aspirin alone in the secondary prevention of different types of thrombotic arterial disease. Results of randomized, placebo-controlled trials of aspirin in patients with confirmed cardiovascular disease were abstracted and synthesized by the Mantel–Haenszel method. We defined three cardiovascular disease groups according to the qualifying disease at entry: coronary artery disease (CAD), cerebrovascular disease (CRVD), and peripheral arterial disease (PAD). Results are given as odds ratios (OR) and 95% confidence intervals (95% CI). Compared with placebo, aspirin decreased significantly the risk of all-cause death in CAD and CRVD (OR = 0.80, 95% CI 0.75–0.86 and 0.91, 95% CI 0.85–0.98, respectively), and of vascular events in CAD, CRVD, and PAD (OR = 0.71, 95% CI 0.67–0.76, 0.87, 95% CI 0.82–0.93, and 0.50, 95% CI 0.29–0.88, respectively). The risk of non-fatal stroke was decreased in the CAD, CRVD, and PAD (OR = 0.64, 95% CI 0.50–0.83, 0.81, 95% CI 0.74–0.89, and 0.26, 95% CI 0.07–0.94, respectively). The risk of non-fatal myocardial infarction was decreased significantly in the CAD and CRVD (OR = 0.59, 95% CI 0.53–0.67, and 0.63, 95% CI 0.48–0.84, respectively), but not in the PAD (OR = 0.43, 95% CI 0.15–1.25). Aspirin nearly doubled the risk of major bleeds (OR = 1.87, 95% CI 1.51–2.32 for all clinical conditions). This meta-analysis confirms that aspirin decreases the risk of thrombotic events in patients with confirmed disease of the coronary, cerebrovascular, or peripheral artery beds.