Background: Drug provocation tests (DPT) are the criterion standard method for diagnosing nonsteroidal anti-inflammatory drugs (NSAID) and paracetamol hypersensitivity reactions in children. However, there is no consensus in the literature with regard to the duration of DPTs. Objective: The objective was to compare the negative predictive values (NPV) of single- and 2-day DPTs for NSAID and paracetamol hypersensitivity diagnosis in pediatric patients. Methods: We retrospectively evaluated children (ages 1–18 years) with a history of NSAID and paracetamol hypersensitivity. The patients were categorized into two groups based on drug provocation duration: short (single-day test) and extended (test continued on the second day at home). Patients with negative DPT results for the suspected agent were contacted to determine whether they reused the drug and, if so, whether there was a reaction. The NPVs of the DPTs performed for both groups were calculated. Results: The DPT results of 104 patients (53.8% boys) were negative for 116 suspected agents: 67 (57.7%) tested with short DPT and 49 (42.2%) with extended DPT. No significant differences in age, sex, reaction type, or comorbidities were observed between the two groups. In the follow-up, 114 DPTs were performed for 102 patients, of whom 93 used the suspected drug(s) after the tests but none developed a reaction. The NPV was the same for both groups: 100%. Conclusion: To the best of our knowledge, this is the first study to compare the NPVs of single- and 2-day DPTs for children who present with suspected NSAID and paracetamol hypersensitivity. Our results indicate that both approaches have the same NPV and suggest that single-day DPT is sufficient to exclude suspicion of NSAID and paracetamol hypersensitivity in children.