We developed a prototype for measuring physiological data for pulse transit time (PTT) estimation that will be used for ambulatory blood pressure (BP) monitoring. The device is comprised of an embedded system with multimodal sensors that streams high-throughput data to a custom Android application. The primary focus of this paper is on the hardware–software codesign that we developed to address the challenges associated with reliably recording data over Bluetooth on a resource-constrained platform. In particular, we developed a lossless compression algorithm that is based on optimally selective Huffman coding and Huffman prefixed coding, which yields virtually identical compression ratios to the standard algorithm, but with a 67–99% reduction in the size of the compression tables. In addition, we developed a hybrid software–hardware flow control method to eliminate microcontroller (MCU) interrupt-latency related data loss when multi-byte packets are sent from the phone to the embedded system via a Bluetooth module at baud rates exceeding 115,200 bit/s. The empirical error rate obtained with the proposed method with the baud rate set to 460,800 bit/s was identically equal to 0%. Our robust and computationally efficient physiological data acquisition system will enable field experiments that will drive the development of novel algorithms for PTT-based continuous BP monitoring.