Background Artificial intelligence (AI) has potential to streamline interpretation of pH-impedance studies. In this exploratory observational cohort study, we determined feasibility of automated AI extraction of baseline impedance (AIBI) and evaluated clinical value of novel AI metrics. Methods pH-impedance data from a convenience sample of symptomatic patients studied off ( n  = 117, 53.1 ± 1.2 years, 66% F) and on ( n  = 93, 53.8 ± 1.3 years, 74% F) anti-secretory therapy and from asymptomatic volunteers ( n  = 115, 29.3 ± 0.8 years, 47% F) were uploaded into dedicated prototypical AI software designed to automatically extract AIBI. Acid exposure time (AET) and manually extracted mean nocturnal baseline impedance (MNBI) were compared to corresponding total, upright, and recumbent AIBI and upright:recumbent AIBI ratio. AI metrics were compared to AET and MNBI in predicting  ≥ 50% symptom improvement in GERD patients. Results Recumbent, but not upright AIBI, correlated with MNBI. Upright:recumbent AIBI ratio was higher when AET  > 6% (median 1.18, IQR 1.0–1.5), compared to  < 4% (0.95, IQR 0.84–1.1), 4–6% (0.89, IQR 0.72–0.98), and controls (0.93, IQR 0.80–1.09, p  ≤ 0.04). While MNBI, total AIBI, and the AIBI ratio off PPI were significantly different between those with and without symptom improvement ( p  < 0.05 for each comparison), only AIBI ratio segregated management responders from other cohorts. On ROC analysis, off therapy AIBI ratio outperformed AET in predicting GERD symptom improvement when AET was  > 6% (AUC 0.766 vs. 0.606) and 4–6% (AUC 0.563 vs. 0.516) and outperformed MNBI overall (AUC 0.661 vs. 0.313). Conclusions BI calculation can be automated using AI. Novel AI metrics show potential in predicting GERD treatment outcome.