Physical activity (PA) is globally recognized as a pillar of general health. Step count, as one measure of PA, is a well known predictor of long-term morbidity and mortality. Despite its popularity in consumer devices, a lack of methodological standards and clinical validation remains a major impediment to step count being accepted as a valid clinical endpoint. Previous works have mainly focused on device-specific step-count algorithms and often employ sensor modalities that may not be widely available. This may limit step-count suitability in clinical scenarios. In this paper, we trained neural network models on publicly available data and tested on an independent cohort using two approaches: generalization and personalization. Specifically, we trained neural networks on accelerometer signals from one device and either directly applied them or adapted them individually to accelerometer data obtained from a separate subject cohort wearing multiple distinct devices. The best models exhibited highly accurate step-count estimates for both the generalization (96–99%) and personalization (98–99%) approaches. The results demonstrate that it is possible to develop device-agnostic, accelerometer-only algorithms that provide highly accurate step counts, positioning step count as a reliable mobility endpoint and a strong candidate for clinical validation.