Background: The elderly people generally have poor tolerance to drugs and an increased risk of adverse effects. Our study was designed to determine the effect and safety of Helicobacter pylori (H. pylori) eradication treatment based on molecular pathologic antibiotic resistance in Chinese elderly people over the age of 60 years. Methods: A total of 364 people were retrospectively analyzed, including 113 older people over 60 and 251 young and middle-aged people in the age of 20-59 years. Real-time PCR detection and conventional PCR and sequencing method were used for drug susceptibility testing. As the main outcome measure, the eradication rates (ERs) with their 95% confidence intervals (CIs) were analyzed by intention to treat (ITT) and per protocol (PP). For the safety of therapy, adverse events were analyzed. Results: For the total people, the resistance rates to clarithromycin (CLR), amoxicillin (AMX), fluoroquinolone (FLQ) and tetracycline (TET) were 65.06%, 7.54%, 61.39% and 20.37%, respectively. After they were divided into two groups, the resistance rates were 62.39% (CLR), 9.09% (AMX), 69.64% (FLQ) and 22.45% (TET) in the 113 older people over 60, and 66.26%, 6.85%, 57.66% and 19.47% in the 251 young and middle-aged people in 20-59. By the ITT analysis, the ERs were 92.04% (95% CI, 86.97-97.10%, n=113) in the older people and 92.43% (95% CI, 89.14-95.73%, n=251) in the young and middle-aged people. By the PP analysis, the ERs were 96.30% (95% CI, 92.68-99.92%, n=108) and 94.69% (95% CI, 91.87-97.52%, n=245), respectively. No significant differences were shown both in the ITT analysis (P=0.896) and in the PP analysis (P=0.517). The three most common adverse events were black stool, dysgeusia and diarrhea, and no serious adverse event was reported. Conclusion: H. pylori eradication treatment based on molecular pathologic antibiotic resistance showed good effect and safety in Chinese elderly people.