The German "Clean Hands Campaign" (an adaptation of the WHO "Clean Care is Safer Care" programme) to promote hand hygiene among hospital personnel at Hannover Medical School (MHH, Medizinische Hochschule Hannover), known as Aktion Saubere Hände (ASH), met with initial success. By 2013, however, compliance rates with hygienic hand disinfection in the hospitals ten intensive care units (ICUs) and two hematopoietic stem cell transplantation units (HSCTUs) had relapsed to their initial levels (physicians: 48%; nurses: 56%). The cluster- randomized controlled trial PSYGIENE was conducted to investigate whether interventions tai - lored in ways suggested by research in behavioral psychology might bring about more sustainable improvements than the ASH. The "Health Action Process Approach" (HAPA) compliance model specifies key psychological determinants of compliance. These determinants were assessed among health care workers in the ICUs and HSCTUs of the MHH by questionnaire (response rates: physicians: 71%; nurses: 63%) and by interviews of the responsible ward physicians and head nurses (100%). In 2013, 29 tailored behavior change techniques were implemented in educational training sessions and feedback discussions in the six wards that constituted the intervention arm of the trial, while ASH training sessions were provided in the control arm. The compliance rates for 2014 and 2015 (the primary outcomes of the trial) were determined by nonparticipating observation of hygienic hand disinfection, in accordance with the World Health Organizations gold standard. The two groups did not differ in their baseline compliance rates in 2013 (intervention: 54%, control: 55%, p = 0.581). The tailored interventions led to increased compliance in each of the two follow-up years (2014: 64%, p<0.001; 2015: 70%, p = 0.001), while the compliance in the control arm increased to 68% in 2014 (p<0.001) but fell back to 64% in 2015 (p = 0.007). The compliance increases from 2013-2015 and the compliance rate in 2015 were higher in the intervention arm (p<0.005). This was mainly attributable to the nurses behavior, as the corresponding parameters for physicians did not differ significantly between the two study arms in stratified analysis. Tailored interventions based on behavioral psychology principles led to more sustainable increases in compliance with hand hygiene guidelines than ASH training sessions did. This was true among nurses, and thus also for hospital ward personnel as a whole (i.e., nurses and physicians combined). Further studies are needed to identify more target group-specific interventions that may improve compliance among physicians.