Background <p>Several case reports describe new onset or relapsed nephrotic syndrome (NS) after COVID-19 mRNA vaccination. However, there have been no systematic studies in children.</p> Methods <p>In this single-center, retrospective cohort study, we used our electronic health record registry to identify patients with NS who received ≥ 1 dose of COVID-19 vaccine from 12/2020 to 12/2022. For each patient, we determined number of relapses in the 180 days pre- and 60 days post-vaccination. Conditional logistic regression was used to assess risk of relapse after vaccination. Linear regression was used to estimate the mean difference between individual-level post- and pre-vaccine relapse rates.</p> Results <p>Ninety-five patients with relapsing NS were included (median age 12 years, 43% female). Their clinical phenotype was as follows: 33% infrequent relapsing, 52% frequently relapsing (FR)/steroid-dependent (SD)/secondarily steroid responsive (SSR), and 16% steroid-resistant. Twenty-five patients (26%) relapsed in the pre-vaccine period, 17 (18%) had ≥ 1 relapse post-vaccination, and 78 (82%) had no relapse documented after COVID-19 vaccination. There was no significant difference in the risk of relapse after versus before vaccination (odds ratio 0.43, <i>p</i> = 0.08), and no significant difference in relapse rates after versus before vaccination (mean difference 0.08 per 100 patient-days, <i>p</i> = 0.39), overall or by phenotype. Of post-vaccine relapses, 94% occurred among the FR/SD/SSR group. Five patients met criteria for new onset NS presenting ≤ 60 days after receipt of the COVID-19 vaccine.</p> Conclusions <p>In a systematic pre/post comparison of individual-level relapse frequency, we found no significant difference in risk or rates of relapse after COVID-19 vaccination in children with NS.</p> Graphical abstract <p></p>