Our aim was to determine the independent predictors of minimum clinically important difference (MCID) in quality of life (QOL) after selective amygdalohippocampectomy (SAH) among Chinese patients with refractory mesial temporal lobe epilepsy (MTLE). We conducted a prospective study and enrolled 50 consecutive patients with refractory MTLE who underwent SAH after their presurgical evaluations. The variables independently associated with MCID in the Quality of Life in Epilepsy Inventory-31 (QOLIE-31) overall score 1 year after SAH were analyzed by multiple binary logistic regression analysis. Significant improvements in the QOLIE-31 overall score and all subscale scores were observed after SAH (p < 0.001). Among 50 patients with refractory MTLE, 78% reached the criteria for MCID of QOL overall score after SAH. In the multiple binary logistic regression model, the presurgical independent predictors of significant improvement by MCID in QOL were absence of depression diagnosis (adjusted odds ratio [OR] = 8.391, 95% confidence interval [CI] = 1.240–56.776, p = 0.029) and good cognitive function (adjusted OR = 8.427, 95% CI = 1.115–63.670, p = 0.039); the postoperative independent predictor was seizure freedom (adjusted OR = 8.477, 95% CI = 1.195–60.122, p = 0.032). The sensitivity and specificity for significant improvement in the QOL were 97.4% and 45.5% respectively, with an overall model accuracy of 86.0%. Presurgical depression, cognitive function, and postsurgical seizure freedom are independent predictors for meaningful improvement in QOL after SAH among the Chinese patients with refractory MTLE. Preoperative evaluation of patients with refractory MTLE should consider the cognitive dysfunction and psychological disorders. • We applied the MCID concept to determine significant improvement in the QOL. • Significant improvement in the QOL is demonstrated one year after epilepsy surgery. • Depression and cognitive function are independent presurgical predictors for meaningful improvement in QOL. • Seizure freedom is an independent postsurgical predictor for meaningful improvement in QOL. • Neuropsychological evaluations should be routinely administered before epilepsy surgery. [ABSTRACT FROM AUTHOR]