INTRODUCTION: Multiple observational studies have reported associations between long-term PPI use and adverse events particularly in the elderly leading to increased morbidity and healthcare utilization. We examined the trend, per-patient expenditures and healthcare resource utilization associated with PPI use in non-institutionalized elderly in the United States (US). METHODS: We conducted a cross-sectional study using data from the Medical Expenditure Panel Survey (MEPS) from 2006 to 2015. A Cochrane Armitage trend analysis was performed on elderly (>65 years old) participants in the US self-reporting PPI use during this period. Trend in PPI use were compared by race, socioeconomic, and educational status of participants. Weighted logistic regression was used to explore the association between PPI use, healthcare utilization and expenditures, adjusted for relevant sociodemographic factors and comorbidities. RESULTS: We identified 32 790 elderly participants with data on PPI use representing ≅38.8 million US elderly population. Trend in PPI use increased from 20.6% (95% CI, 19.2%-22.1%) in the 2006-07 cohort to 22.7% (95% CI, 20.7%-24.4%) in the 2014-15 cohort (P = 0.07, Figure 1). Women reported higher rates of PPI use compared to men (22.5% vs 19.8%, P < 0.001). Interestingly, PPI use significantly increased in Hispanics in the study period (Figure 1). Hispanic participants had the highest rates of PPI use (22.9%), followed by non-Hispanic Whites (21.7%), African-Americans (19.7%) and lowest in Asians (16.7%) (P < 0.001). PPI use was most prevalent in elderly residing in the Southern US (P = 0.006), and significantly higher in very low-income earners (P < 0.001), and those with less than high school education (P < 0001) [Table 1]. Over the 10-year period, we found an increasing trend in PPI use among these subpopulations (Figure 1). Participants reporting PPI use were more likely to have ER visits (AOR: 1.76; 95% CI, 1.55-2.01) and hospitalizations (AOR: 1.86; 95% CI, 1.49-1.77) compared to non-PPI users even after adjusting for potential confounders (Table 2). Expectedly, this increased resource utilization among PPI users resulted in higher health-related costs with an excess of $3,483 (95% CI, $2815-$4151) in mean total annual healthcare expenditures compared to non-PPI user. CONCLUSION: Despite reports of adverse events associated with PPI use especially in the elderly, trend in PPI use is increasing particularly among elderly Hispanic patients, low-income earners, and those with less than a high school education.