Background: Complex regional pain syndrome (CRPS) following stroke aggravates morbidity. CRPS is categorized as CRPSI when no clear nerve injury is defined, and CRPSII when associated with clear nerve injury. Aim: To compare the effect of prednisolone with that of piroxicam in patients with CRPSI following stroke. Design: Randomized controlled trial. Methods: Patients with CRPSI fulfilling the inclusion criteria (n = 60) underwent a detailed neurological examination, cranial CT scan, radiograph of chest and shoulder joint, blood counts and serum chemistry. Severity of stroke was assessed by the Canadian Neurological Scale (CNS), CRPS by scoring sensory, autonomic and motor symptoms, and activity of daily living by Barthel index (BI) score. Patients were randomly assigned prednisolone 40 mg or piroxicam 20 mg daily, and outcome was assessed at 1 month on the basis of CRPS and BI score. Results: Mean patient age was 56 years and 20 were female. Baseline clinical and radiological parameters were comparable between the two groups. In the prednisolone group, 83.3% patients showed significant improvement, compared to 16.7% in the piroxicam group. The mean change in CRPS score in prednisolone group was 6.47 (95%CI 4.37–7.36), whereas in piroxicam group it was only 0.47. The mean change in BI score was 7.9 (95%CI 0.82–5.98) in the prednisolone group, and 4.5 in the piroxicam group. Discussion: In this patient group, prednisolone resulted in significant improvement in the symptoms and signs of CRPSI following stroke, compared to piroxicam. Both drugs produced an improvement in the BI score.