Objectives: This observational case-control study aimed to assess the safety and efficacy of oral Naproxen as an alternative to oral Aspirin/acetylsalicylic acid (ASA) for treating acute rheumatic fever (ARF). Methodology: Patients meeting the revised Jones criteria 2015 for ARF were enrolled from November 2018 to May 2019 at a single tertiary care Children’s Hospital. They were divided into two groups: Group-A receiving ASA (control) and Group-B receiving Naproxen (case). Primary outcome measures included the number of days until complete resolution of arthralgia or arthritis, while secondary outcome measures included resolution of fever and normalization of erythrocyte sedimentation rate (ESR). Results: Sixty-four consecutive patients with ARF were enrolled, with 32 in each group, matched for age and gender. The majority (80%) had recurrent ARF. Median age at presentation was similar in both groups. ESR levels did not differ between the groups at admission or at the end of treatment. Median time for resolution of fever was 9(6-11) days in Group-A and 7.5(5-10) days in Group-B. Resolution time for arthritis was similar in both groups, with a median of 3(2-4) days. Gastric pain and vomiting were significantly lower in Group-B than in Group-A. Overall response rates were comparable between the groups. Conclusion: Naproxen demonstrates equal effectiveness, safety, and better tolerance compared to Aspirin in treating ARF patients.