Radial artery occlusion (RAO) is an infrequent, asymptomatic, complication of transradial catheterization and probably 1 of the few. Intravenous heparin and patent hemostasis lower its incidence. A possible local effect of intra-arterially administered heparin during transradial procedures has not been evaluated. We studied 500 consecutive patients randomized to an intravenous group (n = 250), receiving 50 U/kg of unfractionated heparin (maximal dose 5,000 U) intravenously, and an intra-arterial group (n = 250) receiving the same dose intra-arterially. All patients received a vasodilator "cocktail" intra-arterially and underwent cardiac catheterization using a 5F introducer sheath and catheters. The activated clotting time was measured at the end of the procedure. All patients received hemostasis with a radial compression device (TR Band), applied after sheath removal, for 2 hours. A plethysmographic evaluation for RAO was performed at 24 hours and 30 days after the procedure. Early RAO occurred in 5.6% (n = 14) of the intravenous group and 6% (n = 15) of the intra-arterial group. The difference was not statistically significant (chi-square = 0.037, p >0.8). Chronic RAO occurred in 3.2%, (n = 8) of the intravenous group compared to 4% (n = 10) of the intra-arterial group. The difference was not statistically significant (chi-square = 0.231, p >0.6). The activated clotting time was 211 +/- 16 seconds in the intravenous group and 213 +/- 17 seconds in the intra-arterial group, a statistically insignificant difference (t = -1.095, p >0.2). In conclusion, intra-arterial and intravenous heparin administration provide comparable efficacy in preventing RAO, favoring a probable systemically mediated mechanism of action, rather than a local effect.