Postoperative complications after pancreatic surgery are frequent and life-threatening. Current clinical diagnostic strategies involve time-consuming quantification of α-amylase activity in abdominal drain fluid, which is taken on the first and third postoperative day. The lack of real-time data can delay adjustment of medical treatment upon complications and worsen prognosis for patients. We report a bedside portable droplet-based millifluidic device enabling real-time sensing of drain α-amylase activity for postoperative monitoring of patients undergoing pancreatic surgery. Here, a tiny amount of drain liquid of patient samples is continuously collected and co-encapsulated with a starch reagent in nanoliter-sized droplets to track the fluorescence intensity released upon reaction with α-amylase. Comparing the α-amylase levels of 32 patients, 97% of the results of the droplet-based millifluidic system matched the clinical data. Our method reduces the α-amylase assay time to approximately three minutes, which is a major improvement compared to the current clinical standard of several hours in the clinic. Furthermore, the device reveals an order of magnitude improvement in the limit of detection, reaching 7 nmol/s·L. The presented droplet-based diagnostics platform can be extended for analysis of different body fluids, diseases, and towards a broader range of biomarkers, including lipase, bilirubin, lactate, inflammation, or liquid biopsy markers, setting up new standards in clinical patient monitoring.