Health information technologies (HITs) are widely employed in healthcare and are supposed to improve quality of care and patient safety. However, so far, their implementation has shown mixed results, which might be explainable by understudied psychological factors of human-HIT interaction. Therefore, the present study investigates the association between the perception of HIT characteristics and psychological and organizational variables among 445 healthcare workers via a cross-sectional online survey in Germany. The proposed hypotheses were tested using structural equation modeling. The results showed that good HIT usability was associated with lower levels of techno-overload and lower IT-related strain. In turn, experiencing techno-overload and IT-related strain was associated with lower job satisfaction. An effective error management culture at the workplace was linked to higher job satisfaction and a slightly lower frequency of self-reported medical errors. About 69% of surveyed healthcare workers reported making errors less frequently than their colleagues, suggesting a bias in either the perception or reporting of errors. In conclusion, the study’s findings indicate that ensuring high perceived usability when implementing HITs is crucial to avoiding frustration among healthcare workers and keeping them satisfied. Additonaly healthcare facilities should invest in error management programs since error management culture is linked to other important organizational variables.