AbstractBackgroundMultidrug‐resistant Helicobacter pylori strains are emerging in Southeast Asia. This study evaluates the region's real‐world practice in H. pylori management.Materials and MethodsPhysicians who managed H. pylori eradication in daily practice across 10 Southeast Asian countries were invited to participate in an online questionnaire, which included questions about the local availability of antimicrobial susceptibility tests (ASTs) and their preferred eradication regimens in real‐world practice. An empiric regimen was considered inappropriate if it did not follow the local guidelines/consensus, particularly if it contained antibiotics with a high reported resistance rate or was recommended not to be empirically used worldwide.ResultsThere were 564 valid responses, including 314 (55.7%) from gastroenterologists (GIs) and 250 (44.3%) from non‐GI physicians. ASTs were unavailable in 41.7%. In countries with low and intermediate clarithromycin resistance, the most common first‐line regimen was PAC (proton pump inhibitor [PPI], amoxicillin, clarithromycin) (72.7% and 73.2%, respectively). Regarding second‐line therapy, the most common regimen was bismuth‐based quadruple therapy, PBMT (PPI, bismuth, metronidazole, tetracycline) (50.0% and 59.8%, respectively), if other regimens were used as first‐line treatment. Concomitant therapy (PPI, amoxicillin, clarithromycin, metronidazole) (30.5% and 25.9%, respectively) and PAL (PPI, amoxicillin, levofloxacin) (22.7% and 27.7%, respectively) were favored if PBMT had been used as first‐line treatment. In countries with high clarithromycin resistance, the most common first‐line regimen was PBMT, but the utilization rate was only 57.7%. Alarmingly, PAC was prescribed in 27.8% of patients, ranking as the second most common regimen, and its prescription rate was higher in non‐GI physicians than GI physicians (40.1% vs. 16.2%, p < 0.001).ConclusionsChoosing inappropriate regimens containing antibiotics with high resistance rates is not uncommon in Southeast Asia, especially among non‐GI physicians. In countries with high clarithromycin resistance, the PBMT regimen is underutilized.