Background: Platelet indices (PIs) are platelet parameters that are correlated with platelet activity. Despite being widely available, inexpensive, and feasible; their use in clinical settings is limited. Recently, we developed a new score (EgyDAS), which relies on PIs and assesses disease activity in rheumatoid arthritis (RA). Objectives: This study explored the practicability and validity of EgyDAS in RA with ankle involvement, considering that ankle is neglected in the commonly used DAS28 score. Methods: This comparative case-control study included 2-groups of RA patients, group1 (control): without and group 2: with ankle involvement. Results: Ankle involvement in RA showed no gender or age differences, however, it was associated with higher platelet count, erythrocyte sedimentation rate (ESR), Creactive protein (CRP), platelet distribution width (PDW), visual analogue scale (VAS), tender joint count (TJC), and lower hemoglobin (Hb) and mean platelet volume (MPV). DAS28 categorized a higher proportion of patients to have high disease activity compared with Egy- DAS; moreover, it did not detect those in remission in group 2 patients. Highly significant differences in the 2-scores were observed between the two groups. Further analyses revealed superiority of EgyDAS in assessing disease activity in group 2 patients. Finally, both scores were found correlated together in the study groups. Conclusions: Over or underestimation of RA disease activity could occur when using DAS28. PIs were found correlated with ankle involvement in RA. PIs and EgyDAS are the best tools to assess disease activity in RA patients with ankle involvement. However, the study recommended the use of both scores together.