The digoxin drug has a narrow therapeutic window that requires regular blood concentration monitoring in a tertiary hospital. The concentration of a drug varies due to several factors. The factors may include physiological and biochemical factors, comorbidities, and concomitant medications. The purpose of this study was to analyze the monitoring data of serum digoxin concentration (SDC) using logistic regression and to find the SDC correlated factors. SDC with a cutoff value of 0.9 ng/mL, which corresponds to the proposed safety upper limit by international heart failure recommendations (ACCF/AHA). This cross-sectional study retrospectively analyzed data from 178 patients at Jiande First People's Hospital, including SDC, demographic characteristics, biochemical parameters, comorbidities, and medication use. Patients were stratified into 2 groups based on an SDC cutoff of 0.9 ng/mL (<0.9 vs ≥0.9 ng/mL) to describe population characteristics and perform comparative analyses, including univariate logistic regression. Variables with P < .1 in the univariate analysis were included in a stepwise regression model. Factors with P < .05 which remained in the final model. Among 178 patients, those with SDC < 0.9 ng/mL accounted for 43.26%, while patients with SDC ≥ 0.9 ng/ml comprised 56.74%. The median SDC was 1.05 ng/ml (IQR: 0.54, 1.60). Univariate analysis revealed several factors significantly associated with SDC levels. The results of multivariate logistic regression indicated that age (odds ratio [OR] = 1.10, 95% confidence interval [CI]: 1.05-1.15, P < .001), chloride ion (Cl-) (OR = 0.87, 95% CI: 0.81-0.94, P < .001), high-density lipoprotein cholesterol (HDLC) (OR = 0.08, 95% CI: 0.02-0.30, P < .001), blood urea nitrogen (BUN) (OR = 1.15, 95% CI: 1.07-1.25, P < .001), Deslanoside (OR = 5.41, 95% CI: 1.39-21.15, P = .015), and hypoglycemic drugs (OR = 0.30, 95% CI: 0.10-0.89, P = .030) were all significantly associated with SDC levels. Age, Cl-, HDLC, BUN, Deslanoside, and hypoglycemic drugs are independent factors influencing SDC. These findings provide valuable references for the rational clinical use of digoxin.