Chronic stress is a major risk factor for impaired health among employees and represents a significant economic burden on organizations and society as a whole. The implementation of information and communication technologies (ICTs) holds considerable potential to improve stress-relevant working conditions and reduce chronic stress among employees. However, methodologically sound research examining effects of ICT implementation on stress-relevant working conditions, chronic stress, and stress-related health outcomes remains limited. This longitudinal, multi-method, control-group biopsychological implementation study sought to address this gap by examining (1) how the introduction of an electronic lab notebook (ELN) influences stress-relevant working conditions, (2) how these changes affect biopsychological stress indicators of chronic stress (measured via questionnaires, heart rate variability, hair cortisol/cortisone concentrations) and health, and (3) the potentially moderating role of individual and ELN-related characteristics. Over 17-months, we studied two medical research laboratories from different German university hospitals at four measurement points (T0–T3). The ELN was implemented in one laboratory (lab 1 ; T0: n  = 23 employees; M  = 33.35 years, SD  = 8.61 years, 39.1 % male), while the second laboratory (lab 0 ; T0: n  = 21 employees; M  = 36.43 years, SD  = 9.44 years, 23.8 % male) served as a control group and did not adopt the ELN between T0 and T1. Multi-level analyses revealed (1) significant ELN-related changes in stress-relevant working conditions, (2) corresponding changes in biopsychological stress indicators, and (3) moderating effects of individual and ELN characteristics. Although not all effects remained significant after Benjamini-Hochberg correction, the findings provide initial evidence of the influence of ELN implementation on stress-relevant working conditions and chronic stress. These results offer valuable insights for optimizing future ICT implementation processes.