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BACKGROUND The management of De Quervain's disease is determined more by Intuition than scientific data. The choice of first line conservative option for the management of De Quervain's disease is still a topic of debate. AIM To evaluate the effectiveness of therapeutic ultrasound with or without spica splint in the management of De Quervain's disease (DQD). DESIGN Randomized controlled trial (RCT). SETTING Outpatient department of Al-Nafees Medical College Hospital, Islamabad, Pakistan. POPULATION Thirty patients who had the history of the De Quervain's disease for at least 6 months were enrolled in the study. The ages of the patient were 30-50 year. The population included housewives, maids, painters, and teachers. METHODS Thirty patients were divided into two groups. The control group was treated with therapeutic ultrasound while in the experimental group thumb spica splitting was also added. The data was collected from the subjects through Quick Disabilities of the Arm, Shoulder and Hand questionnaire. The demographic data was presented in the form of tables. Intervention-induced changes within the groups were investigated using paired sample t-test while independent sample t-test was used to compare the two groups. RESULTS Significant changes within both groups (p ≤ 0.05) were observed as a result of intervention. Additionally, significant differences in some instrument items were found between experimental and control group (p ≤ 0.05) after intervention. However, some items did not demonstrate significant changes in both groups likely because there was no effect of De Quervain's disease on those items before the intervention. CONCLUSION The results showed that the use of therapeutic ultrasound and spica splint together is more effective than using therapeutic ultrasound alone in the conservative management of De Quervain's disease. CLINICAL REHABILITATION IMPACT This study provides evidence to the relevant clinicians and professionals on the utility of therapeutic ultrasound combined with thumb spica splint in the conservative management of DQD.