Background: Nephrotic syndrome is the most common glomerular disease affecting children, characterized by heavy proteinuria, edema, hypoalbuminemia, and hyperlipidemia. The mainstay treatment is with prednisolone, whose response is of prognostic significance. Steroid response rates vary across geographical regions, which may be due to the role of genetic and environmental risk factors among different ethnic groups. There is a paucity of data on response to treatment with prednisolone in pediatric patients with nephrotic syndrome in the Tigray region, Northern Ethiopia. Objectives: To assess the pattern of response to prednisolone in pediatric patients treated for nephrotic syndrome at Ayder Comprehensive Specialized Hospital from 2014 to 2019. Methods: A record-based retrospective study was conducted at Ayder Comprehensive Specialized Hospital Mekelle City, Ethiopia. Data was collected and recorded on a predesigned form. Sixty-three patients fulfilled the inclusion criteria, whose data was entered, coded, and analyzed using the statistical software package (SPSS) version 20. Variables of interest included age, gender, blood pressure, presence of hematuria, acute kidney injury, biopsy, secondary causes of nephrotic syndrome, and response to steroid therapy. Data was presented in tables and graphs. Results: The age of the patients ranged from 1 - 17 years, with a median age of 3 years. Fifty-one patients (81%) were males, with a male to female ratio of 4.2:1. Hematuria was present in 66.7%, whereas hypertension was seen in 49.2% of the patients. Thirty-nine patients (61.9%) were responsive to prednisolone, 24 cases (38.1%) were resistant, 8 (20.5%) were steroid-dependent and 19 (48.7%) had relapses. Younger age (AOR 16.671, 95% CI: 1.645 - 168.904 P = 0.017) and high cholesterol values (AOR 1.013, 95% CI: 1.005 - 1.021 P = 0.01) were independent factors associated with steroid responsiveness. Conclusions: The steroid response rate in this study is similar to that in Asian and some African countries. Most patients in our hospital had atypical features of nephrotic syndrome. Younger age and high cholesterol levels were independent factors affecting steroid response.