Acetylsalicylic acid (ASA) hypersensitivity represents a clinical challenge in acute coronary syndrome (ACS) patients urgently requiring ASA for antiplatelet therapy. ASA desensitization has been reported with successful outcomes in cardiac patients. The aim of this review is to determine the safety and efficacy of ASA desensitization therapy in ACS patients. A PubMed database search was conducted for articles containing combinations of keywords, "aspirin desensitization" or "aspirin hypersensitivity" and "acute coronary syndrome" between January 1, 1990 and August 1, 2018. The primary end point was desensitization protocol success. Secondary end points included hypersensitivity adverse events and ASA discontinuation due to hypersensitivity adverse events at follow-up. Fifteen reports consisting of 480 ACS patients with previous hypersensitivity to ASA were included. The pooled desensitization success rate was 98.3% (95% confidence interval: 97.2% to 99.5%). There was no statistical difference in outcomes between protocols ≤ 2 hours and > 2 hours in duration (96.3[92.3 to 100.3]% vs 97.2[94.6 to 99.8]%; p = 0.71). Protocols with > 6 dose escalations were associated with higher success rates compared to those with ≤ 6 doses (99.2[97.9 to 100.4]% vs 95.4[93 to 97.8]%; p = 0.007). At follow-up between 1 and 46 months (mode 12 months), zero hypersensitivity adverse events were reported. Consequently, no ASA discontinuations were related to hypersensitivity adverse events. In conclusion, ASA desensitization therapy is safe and effective in patients with ACS. Protocols with > 6 dose escalations may be optimal for ASA desensitization in ACS patients.