Background: Delirium is a pathobiological brain process that is frequently observed in Intensive Care Unit (ICU) patients, and is associated with longer hospitalization as well as long-term cognitive impairment. In neurological ICU patients, delirium may be more treatment-resistant due to the initial brain injury. This study examined the effects of a multicomponent non-pharmacological nursing intervention program on delirium in neurological ICU patients. Methods: A single-center interrupted time series trial was conducted in adult neurological ICU patients at high risk for developing delirium who were non-delirious at admission. A multicomponent nursing intervention program focusing on modifiable risk factors for delirium, including the optimalization of vision, hearing, orientation and cognition, sleep and mobilization, was implemented as the standard of care, and its effects were studied. The primary outcome was the number of delirium-free and coma-free days alive at 28 days after ICU admission. The secondary outcomes included delirium incidence and duration, ICU and hospital length-of-stay and duration of mechanical ventilation. Results: Of 289 eligible patients admitted to the ICU, 130 patients were included, with a mean age of 68 ± 11 years, a mean APACHE-IV score of 79 ± 25 and a median predicted delirium risk (E-PRE-DELIRIC) score of 42 [IQR 38-50]). Of these, 73 were included in the intervention period and 57 in the control period. The median delirium- and coma-free days alive were 15 days [IQR 0-26] in the intervention group and 10 days [IQR 0-24] in the control group (level change -0.48 days, 95% confidence interval (95%CI) -7 to 6 days, p = 0.87; slope change -0.95 days, 95%CI -2.41 to 0.52 days, p = 0.18). Conclusions: In neurological ICU patients, our multicomponent non-pharmacological nursing intervention program did not change the number of delirium-free and coma-free days alive after 28 days.