Background <p>Although single-daily cyclosporine may offer an effective therapeutic option with increased compliance and reduced nephrotoxicity, response predictors and long-term outcomes following this regimen remain unclear in children with steroid-dependent nephrotic syndrome.</p> Methods <p>A retrospective study was conducted between October 2005 and December 2021 on children with steroid-dependent nephrotic syndrome caused by minimal change disease (MCD) who were treated with preprandial single-daily cyclosporine to maintain 2-h post-dose levels of 500–700&#xa0;ng/mL. The primary endpoint was the time to treatment failure after single-daily cyclosporine initiation. The secondary endpoint was the long-term outcome at last visit.</p> Results <p>After initiating single-daily cyclosporine therapy in 48 children, 31 patients, including 18 who did not experience relapse during treatment, were able to discontinue steroids (response group), while 17 patients experienced treatment failure. The median time to the first relapse after nephrotic syndrome diagnosis was significantly shorter in the treatment failure group than in the response group (2.1 vs. 4.3&#xa0;months, <i>p</i> = 0.014). Multivariable Cox proportional hazard regression analysis identified two independent risk factors for treatment failure: early first relapse &lt; 2.2&#xa0;months after nephrotic syndrome diagnosis (hazard ratio: 7.79, 95% confidence interval: 2.29–26.48, <i>p</i> = 0.001) and higher prior relapse rate (hazard ratio: 1.41 per episode increase, 95% confidence interval: 1.07–1.86, <i>p</i> = 0.016). None of the patients progressed to chronic kidney disease Stage 3 or higher.</p> Conclusions <p>Single-daily cyclosporine may offer a promising treatment option for children with steroid-dependent nephrotic syndrome caused by MCD, particularly for those who do not experience early relapse following nephrotic syndrome diagnosis and have lower prior relapse rate.</p> Graphical abstract <p></p>