The important role of platelets in thrombosis makes inhibitors of their reactivity potentially useful therapeutically. A number of laboratory tests have been identified which measure platelet reactivity, but it is not clear which test and which drug effect will correlate with thrombosis and thrombosis prevention. Platelet survival (SURV) correlates with thromboembolism in patients with valvular heart disease and is shortened in several other diseases. Therefore, it is of interest to identify drugs which prolong shortened SURV. Patients with arterial and venous thromboembolism and shortened SURV (51Chromium) were treated with platelet suppressants and restudied after 12 weeks. Sulfinpyrazone prolonged SURV(2.4±.04 to 3.1 ±.06 days; p < 0.001; n = 94; average ± SEM; normal, 3.7±.04 days) and 68 (72%) had some prolongation and 39 (42%) had normalization (> 3.3 days). Dipyridamole (100 mg qd) combined with aspirin (1200 mg qd) prolonged SURV (2.6±.11 to 3.2±0.12 days; p < 0.001; n = 13) and 9 of 13 (69%) had prolongation and 6 (46%) had normalization. Clofibrate altered SURV (2.6±.09 to 3.4±.14days;p < 0.001; n = 12) and 10 of 12 (83% ) had prolongation and normalization occurred in 6 (50%). Aspirin (1200 mg qd), cyproheptadine (32 mg qd) and propranolol (160 mg qd) failed to alter SURV.Thus, of drugs which alter in vitro tests of platelet reactivity, only sulfinpyrazone, dipyridamole and clofibrate improve shortened SURV.