The Ticlopidine Microangiopathy of Diabetes study (TIMAD), a randomized, double-masked, placebo-controlled trial, assessed the effect of this antiplatelet agent (ticlopidine hydrochloride) in reducing the progression of nonproliferative diabetic retinopathy in 435 patients followed up for 3 years. The mean yearly increase in definite microaneurysms on fluorescein angiograms was significantly higher (P = .03) in the placebo group (1.44 +/- 4.67) than in the ticlopidine group (0.48 +/- 5.79). Significance was limited to primary analysis using a quality angiographic coefficient for definite microaneurysms in patients with at least three readable angiograms over a 3-year period. Ticlopidine was significantly beneficial to insulin-treated diabetic patients, inducing a sevenfold reduction of the yearly microaneurysm progression (0.23 +/- 6.66) compared with the placebo (1.57 +/- 5.29) (P = .03). Among insulin-treated diabetic patients, fewer had development of new vessels in the ticlopidine group than in the placebo group, at borderline statistical significance (P = .056). Overall retinopathy progression was significantly less severe in the ticlopidine group (P = .04). Adverse reactions associated with ticlopidine included neutropenia (severe in one patient) with no clinical complications, diarrhea, or rash. This study demonstrated that ticlopidine slows down the progression of nonproliferative diabetic retinopathy.