Objective To investigate the resistance rate of Helicobacter pylori (Hp) to clarithromycin and its correlation with point mutations in 23S rRNA gene. Methods Hp was cultured from gastric biopsy specimen obtained from 189 patients undergoing upper gastrointestinal endoscopy. The DNA of 11 clarithromycin sensitive Hp and 19 clarithromycin resistant Hp was extracted, and 23S rRNA was amplified and sequenced. Results The rate of clarithromycin resistance in cultured Hp was 29. 2%. Point mutations in 23S rRNA gene were found in 17 clarithromycin resistant Hp strains. The proportion of A to G mutation was 36.8%, G to A of 21.5%, C to T of 15.8%, A to C of 10.5% and T to C of 5.3%. No point mutation in 23S rRNA was detected in other 2 clarithromycin resistant and 11 sensitive Hp strains. Conclusion The resistance to clarithromycin is common in Hp, and point mutations in 23S rRNA gene of Hp are frequent in clarithromycin resistant strains, with most prevalent mutations of A to G and next G to A.