OBJECTIVES: Gastroesophogeal reflux disease (GERD) is a common disease affecting 10-20% of the US adult population.  The objective of this study was to estimate the prevalence of refractory GERD and associated direct medical costs using real-world data.  METHODS: Adult patients with GERD initiating a GERD medication were identified using the MarketScan Research Databases (2004-2009) and evaluated in the twelve months before and after GERD medication initiation.  Refractory GERD was evaluated using an eight point scale where one point was given for each of the following: doubling GERD medication dose (including BID), adding another GERD medication, switching GERD medications, GERD-related procedure receipt, GERD-related surgery receipt, excess GI-related outpatient visits (>2), excess GERD-related office visits (>2), or GI-related ER visits.  Patients were determined to have refractory GERD if they had 2 or more points.  Annual unadjusted and multivariate adjusted GERD-related costs (i.e., claims with a GERD diagnosis) and all-cause costs were reported in 2009 dollars for patients with and without refractory GERD. RESULTS: A total of 135,139 GERD patients were analyzed (mean age= 52.9 (SD=14.5) years, 44% male). Approximately one-third (31%) of patients had refractory GERD.  Versus patients with non-refractory GERD, refractory GERD patients were more likely to be female (59% vs. 55%, p<0.001) and had a higher Deyo Charlson Comorbidity score after GERD medication initiation (0.78 vs. 0.56, p<0.001); average age was similar in both groups.  Compared to non-refractory GERD patients, refractory GERD patients had higher total all-cause costs ($18,088 (SD=$36,220) versus $11,044 ($22,985), p<0.001) and higher GERD-related costs ($2,022 (SD=$2,236) versus $1,172 (SD=$1,117), p<0.001).  After controlling for demographic and clinical characteristics, refractory GERD was associated with an additional $7,089 (SD=$7,705) in total costs and $845 (SD=$111) in GERD-related costs. CONCLUSIONS: Refractory GERD is a common disease that may be associated with increased medical resource utilization and associated cost.