Objective: To compare the casting with methylprednisolone acetate injection versus casting alone in de-quervain’s tenosynovitis treatment. Place and Duration of Study: This was a cross-sectional study conducted at Shaikh Zayed Hospital, Lahore from May 2022, to October 2022. MATERIAL AND METHODS: The sample size of 150 participants was determined based on power analysis to detect a clinically significant difference between the two treatment groups with a predetermined level of statistical significance and power. Participants were randomly assigned to two groups: Group A received Casting with Methylprednisolone Acetate Injection, while Group B underwent Casting alone. Informed consent was obtained from all participants before inclusion in the study. Group A participants received a single injection of Methylprednisolone Acetate into the affected area followed by the application of a cast. Group B participants received casting alone without any pharmaceutical intervention. The casting period for both groups was standardized, and participants were closely monitored throughout the treatment duration. RESULTS: The participants in Group A, receivng Cast + Inj., were on average 42.5 years old (SD = 8.2), while those in Group B, receiving Cast alone, were slightly older on average at 43.2 years (SD = 7.5). Gender distribution showed that 62.66% of participants in Group A were female, whereas 60.0% were female in Group B. Participants in Group A, receiving Cast + Inj., experienced a higher level of pain reduction on the Visual Analog Scale, with a mean of 7.2 (SD = 1.5), compared to Group B, which had a lower pain reduction mean of 5.5 (SD = 2.0). Thumb mobility improvement was notably higher in Group A at 92%, while in Group B, it was 75%. CONCLUSION: In conclusion, our study suggests that the combined intervention of Casting with Methylprednisolone Acetate Injection holds promise for achieving superior outcomes in the treatment of De-Quervain's Tenosynovitis compared to treatment modalities evaluated in prior studies.