Background and purpose: About half of the world’s population is infected with Helicobacter pylori (H. pylori). But, the efficacy of therapeutic regimens decreases over time due to increasing resistance of H. pylori to antibiotics. This research aimed at evaluating the efficacy of two triple therapy regimens. Materials and methods: This tudy was performed in Sari Imam Khomeini Hospital, 2016-2017. One hundred forty patients with peptic ulcer disease and naïve H. pylori infection were randomly divided into two groups to receive either 10-day standard triple therapy (Pantoprazole 40 mg, Amoxicillin 1 gr, and Clarithromycin 500mg, all twice daily) or 10-day Levofloxacin-containing triple therapy (Pantoprazole 40 mg BD, Amoxicillin 1000mg BD, and Levofloxacin 500 mg/daily). Eight weeks after the treatment, H. pylori eradication was assessed by 14C- urea breath test. Results: A total of 133 patients completed the study. According to intention to treat analysis (ITT), H. pylori eradication rates were 75.7% (95% CI: 65.7%-85.7%) and 58.8% (95% CI= 47.1%-70%) in standard and Levofloxacin-containing therapies, respectively. Also, per-protocol eradication rates were 83% (95% CI: 74%-92%) and 61% (95% CI= 49%-73%), respectively. The rates of severe adverse effects of therapy were 7.1% and 2.9% in the aforementioned groups, respectively. Conclusion: Both Clarithromycin- and Levofloxacin-containing triple therapies do not seem to be suitable options for first-line H. pylori eradication in Iran. We suggest using Clarithromycin in quadruple regimens and reserve Levofloxacin to be used in second-line eradication regimens, as recommended by Maastricht V Consensus Report.   (Clinical Trials Registry Number: IRCT2015110224825NI)