Background: Primary percutaneous coronary intervention (PCI) has been shown to be the most effective reperfusion strategy in the treatment of acute myocardial infarction (AMI). Aim of the Work:To investigate the association the effectiveness of a combination therapy (pretreatment with high dose atorvastatin and Intra Coronary tirofiban) for the prevention of noreflow in patient with acute STEMI will undergo primary PCI. Patients and Methods: This study enrolled 100 patients admitted with first acute STEMI and at high clinical risk for no Reflow. High risk patients (no-reflow score ≥ 8) were randomly divided into a controlled group A (50 patients) received conventional treatment and a combination therapy group B(50 patients) received combination treatment (atorvastatin 80 mg and IC tirofiban).The patient was considered to exhibit a no-reflow phenomenon if blood flow in the IRA was a TIMI≤2 flow despite successful dilatation and absence of mechanical complications such as dissection, spasm or angiographically evident distal embolization after completion of the procedure. Results: The rate of no-reflow was significantly lower in combination therapy group (10 %) compared to control group (36%).Regarding Indirect perfusion outcome: We found that percent of ST resolution and peak CKMB were significantly higher in combination therapy compared to control group (P value = 0.013 – 0.001 respectively).Ejection fraction tend to be higher in the combination therapy group but not statistically significant (P>0.05).Regarding in hospital complication and 30 days MACE; we found that heart failure symptoms were significantly lower in combination group therapy during in hospital stay and at 30 days follow up (3% and 2% respectively). The composite end point of 30 days MACE occur only in 3% in combination therapy group while 10 % in control group (P =0.033). using Kaplan Meier curve for free survival MACE at 30 days there were also significant different regarding free event rate for MACE, log rank =4.737, P =0.030. We also observed that high thrombotic burden (thrombus grade ≥ 4) was independent predictor for angiographic no reflow (p =0.012), and the use of combination therapy were strongly independent predictors for prevention of no reflow (p =0.002) with relative Risk reduction 72.2% and absolute risk reduction = 26%. Conclusion: Combination of pre-procedure high dose atorvastatin and IC bolus tirofiban can effectively reduce the incidence of no-reflow after primary PCI in patients with acute myocardial infarction who are at high risk of no-reflow.Large thrombus load is independent predictor of angiographic no reflow after primary PCI. However, this combination therapy is strong independent predictors for prevention of angiographic no-reflow.