Empiric therapy for Helicobacter pylori infection results in significantly increased antibiotic resistance and decreased eradication efficacy. The genotypic testing of clarithromycin resistance from stool specimens is a promising method for individualized diagnosis and treatment. This study aimed to determine the status of research and application on this method through a systematic review and meta-analysis. PubMed, Embase, MEDLINE, and WAN FANG database were searched for relevant literature. The quality of included diagnostic articles was evaluated using the quality Assessment of Diagnostic Accuracy Studies-2 tool. A bivariate random-effect model was conducted to calculate the diagnostic accuracy of genotypic testing of clarithromycin resistance. A total of 16 diagnostic-related were included and analyzed after exclusions. The pooled sensitivity and specificity of diagnostic meta-analysis were 0.93 (95% confidence interval [CI]: 0.90-0.96) and 0.98 (95% CI: 0.93-1.00), respectively. The area under the curve (AUC) of the summary receiver operating characteristic was 0.97 (95% CI: 0.95-0.98). The genotypic testing in stool samples had heterogeneous sensitivity (Q=37.82, p < .01, I2 = 37.82) and specificity (Q=60.34, p < .01, I2 = 93.72) in detecting clarithromycin resistance. Purification method, stool sample weight, real-time PCR, and antimicrobial susceptibility testing as reference accounted for the heterogeneity of pooled sensitivity, while patient age, purification method, stool sample weight, and real-time PCR for the heterogeneity of pooled specificity. The genotypic testing of clarithromycin resistance from stool specimens is an accurate, convenient, noninvasive, and rapid detection technology, providing a definitive diagnosis of clarithromycin resistance and guiding the rational antibiotic selection.