Self-calibrated Acoustic Local Positioning Systems (ALPS) generally require a high consumption of hardware and software resources to obtain the user’s position at an acceptable update rate. To address this limitation, this work proposes a self-calibrated ALPS based on a software/hardware co-design approach. This working architecture allows for efficient communications, signal processing tasks, and the running of the positioning algorithm on low-cost devices. This fact also enables the real-time system operation. The proposed system is composed of a minimum of four RF-synchronized active acoustic beacons, which emit spread-spectrum modulated signals to position an unlimited number of receiver nodes. Each receiver node estimates the beacons’ position by means of an auto-calibration process and then computes its own position by means of a 3D multilateration algorithm. A set of experimental tests has been carried out where the feasibility of the proposed system is demonstrated. In these experiments, accuracies below 0.1 m are obtained in the determination of the receptor node position with respect to the set of previously-calibrated beacons.