Objective: To explore the influencing factors of rehabilitation treatment effect in patients with first-episode stroke and provide a theoretical basis for clinical practice. Methods: The clinical data of patients with first-episode stroke who received rehabilitation treatment in our hospital from January 2015 to January 2019 were collected and analyzed retrospectively. The Modified Barthel Index (MBI) and Frenchay Activity Scale (FAS) were used to evaluate the rehabilitation treatment effect. Spearman rank correlation analysis was carried out to investigate the relationship between the data characteristics and rehabilitation treatment effect, and univariate and multivariate logistic regression analyses were conducted to explore the independent factors influencing the rehabilitation treatment effect in the first-episode stroke group. Results: In this study, 786 cases of 873 patients with first-episode stroke were included, with an effective inclusion rate of 90.0%. Univariate analysis showed that MBI and FAS scores were statistically different among patients with different ages, history of hypertension, the number of residual symptoms, depression status, attitude towards rehabilitation, starting time of rehabilitation, rehabilitation treatment duration, and family environment scores (all P<0.05). According to the Spearman rank correlation analysis, age, residual symptoms, depressive status, and starting time of rehabilitation were all negatively correlated with MBI score (r = -0.584, -0.683, -0.573, -0.783) and FAS score (r = -0.438, -0.771, -0.552, -0.599), while the scores of MBI (r = 0.683, 0.572, 0.662) and FAS (r = 0.735, 0.603, 0.724) were positively correlated with the scores of rehabilitation treatment attitude, rehabilitation treatment duration and family environment (all P<0.05). Moreover, according to multivariate logistic regression analysis, age, the number of remaining symptoms, depression status, attitude towards rehabilitation treatment, starting time of rehabilitation treatment, rehabilitation treatment duration, and family environment score could independently affect MBI and FAS scores of patients with stroke (all P<0.05). Conclusion: Age, the number of residual symptoms, depression status, attitude towards rehabilitation treatment, starting time of rehabilitation treatment, rehabilitation treatment duration, and family environment score are independent factors for rehabilitation treatment effect in patients with first-episode stroke.