Background Low birth weight (LBW)/prematurity have been proposed as risk factors for the development of kidney disease in adulthood. Whether there is an association between LBW/prematurity and poor renal outcomes in childhood onset nephrotic syndrome remains unknown. Methods Children with nephrotic syndrome diagnosed between 1 and 18 years of age were followed prospectively from 1996 to 2016 at The Hospital for Sick Children ( N  = 377). LBW/prematurity was defined as birth weight < 2500 g or gestational age < 36 weeks. Normal birth weight (NBW) was defined as birth weight ≥ 2500 g. Measures evaluating clinical course of nephrotic syndrome include initial steroid-resistant nephrotic syndrome (SRNS), time to first relapse, and frequently relapsing nephrotic syndrome. Kaplan-Meier survival analysis, logistic regression, and Cox proportional hazards regression were used to determine the association of LBW/prematurity with clinical outcomes. Results Median birth weights in LBW/premature ( n  = 46) and NBW ( n  = 331) children were 2098 g (interquartile range IQR 1700–2325 g) and 3317 g (IQR 2977–3685 g), respectively. Odds of having SRNS were 3.78 (95% confidence interval CI 1.28–11.21) times higher among LBW/premature children than NBW children. An 8% decrease in odds of developing SRNS was observed for every 100 g increase in birth weight (adjusted odds ratio OR 0.92; 95% CI 0.86–0.98). Median time to first relapse did not differ (hazard ratio HR 0.89; 95% CI 0.53–1.16). Conclusions LBW/premature children were more likely to develop SRNS but did not have a difference in time to first relapse with NBW children. Understanding the impact and mechanism of birth weight and steroid-resistant disease needs further study.