Abstract Background Anticoagulation is indicated in patients undergoing trans-radial coronary angiography (CAG) with or without percutaneous coronary intervention (PCI). However, full-dose enoxaparin given before CAG to all patients may cause over-anticoagulation in those without indication for subsequent PCI. Purpose This study prospectively assessed the anticoagulation profile of staged-dose (0.5±0.25 mg/kg) vs. single-dose (0.75 mg/kg) enoxaparin in troponin-negative patients undergoing elective trans-radial PCI. Methods Eligible patients were randomly assigned to the Planned Staged-dose group or the Planned Single-dose group. In the Planned Staged-dose group, enoxaparin 0.5 mg/kg was administered to all patients before CAG and additional 0.25 mg/kg was given only to those undergoing subsequent PCI immediately before PCI. In the Planned Single-dose group, all patients received enoxaparin 0.75 mg/kg before CAG irrespective of their indication for subsequent PCI. Patients undergoing subsequent PCI in each group were defined as Staged-dose and Single-dose groups, respectively. Anti-Xa levels were assessed at 0 min (before) and 10 min after enoxaparin administration (CAG-0min and CAG-10min, respectively), and 0 min (before) and 10 min after the beginning of PCI (PCI-0min and PCI-10min, respectively), and at the end of PCI (PCI-end). Therapeutic anticoagulation was defined as anti-Xa levels of 0.5–1.2 IU/ml before PCI and 0.5–1.8 IU/ml during PCI, respectively. Bleeding was according to the thrombolysis in myocardial infarction (TIMI) criteria. Results In 170 randomized patients, 38 of 85 and 37 of 85 patients were included in the Staged-dose and the Single-dose groups, respectively. The baseline characteristics were well balanced between the two groups. The anti-Xa levels were lower before PCI (CAG-10min: 0.903±0.124 IU/ml vs. 1.303±0.207 IU/ml, p<0.001; PCI-0min: 0.874±0.149 IU/ml vs. 1.215±0.185 IU/ml, p<0.001) and higher during PCI (PCI-10min: 1.207±0.190 IU/ml vs. 1.083±0.157 IU/ml, p=0.004; PCI-end: 1.079±0.237 IU/ml vs. 1.050±0.255 IU/ml, p=0.62) in patients receiving staged-dose vs. single-dose enoxaparin (Figure 1). The percentages of patients with therapeutic anticoagulation were higher before PCI (CAG-10min: 100% [35/35] vs. 30.6% [11/36], p<0.001; PCI-0min: 96.8% [30/31] vs. 54.1% [20/37], p<0.001) and similar during PCI (PCI-10min: 100% [34/34] vs. 100% [36/36], p=1.000; PCI-end: 97.2% [35/36] vs. 100% [36/36], p=1.000) in the Staged-dose vs. the Single-dose group. No TIMI major or minor bleeding occurred within 24 h of randomization in both groups. Conclusions Although both regimens of enoxaparin achieved adequate anticoagulation during the entire course of PCI, the staged-dose compared to the single-dose regimen reduced over-anticoagulation before PCI. The staged-dose enoxaparin would be a superior anticoagulation regimen in patients undergoing trans-radial CAG, especially when the indication for subsequent PCI is unclear. Figure 1. Staged-dose vs. Single-dose Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): 2016 Peking Union Medical College Hospital (PUMCH) Science Fund for Junior Faculty