Background: Cyclooxygenase-2 (COX-2) inhibitors have different chemical structures compared to non-selective NSAIDs and are highly selective for COX-2 enzymes. There are reports of patients with prior NSAID allergy that tolerated COX-2 inhibitors, however data is heterogenous. This review aims to summarise the cross-reactivity rates of COX-2 inhibitors in patients with prior NSAID hypersensitivity in current literature. Methods: Searches were conducted in PubMed and Embase to retrieve English studies on adults with previous NSAID allergy, and had received at least one dose of celecoxib, etoricoxib, or parecoxib. Forty-eight included studies were further divided into 74 sub-studies, with a total of 1,991 patients and 2,546 challenges. Results: Overall risk of allergic reactions to COX-2 inhibitors in patients with previous allergic reactions to NSAIDs was 4.75%, with the lowest reported risk in patients with immunologic-mediated reactions to NSAIDs (2.17%). Higher risk of allergic reactions to celecoxib (6.51%) were observed compared to etoricoxib (3.21%). Most allergic reactions observed were mild. Conclusion: COX-2 inhibitor cross-reactivity is heterogenous across different patient populations with different type of NSAID hypersensitivity. In patients with prior NSAID allergy, careful history taking and discussion of risks with patient is advisable before conducting a challenge with COX-2 inhibitors.