Context. Opioids and sedatives are the cornerstone of symptom management in the end- of-life patients, but undertreatment is a common problem. Although several studies explored the individual effect of opioids, anxiolytics, and antipsychotics on survival, not much is known regarding their combined use. As these drugs share similar and potentially fatal side effects, primarily respiratory depression which occurs more often during night-hours, it is crucial to explore whether their interaction poses a danger for fragile hospice patients. Objectives. To analyze the relationship of a combination of opioids, anxiolytics, and antipsychotics on survival and the change of night-time death percentage. Methods. A retrospective study of 765 consecutive patients admitted to hospice in Croatia over the period of four years (2013- 2017). The main outcome was the total length of survival of hospice patients regarding different drug combination, along with night- time death percentage. Results. Different combinations of opioids, anxiolytics, and antipsychotics were associated with longer survival in hospice compared with patients using no such drugs. When we included different parameters which affected overall survival into a multivariate analysis, only the patients who had the combination of both opioids, anxiolytics, and antipsychotics in their regular therapy were associated with longer survival in hospice (11 vs. five days, hazard ratio 0.54, P < 0.001). No combination of opioids, anxiolytics, and antipsychotics significantly changed the night-time death percentage. Conclusion. This research supports the safety of opioids, anxiolytics, and antipsychotics in the hospice setting when used both individually as well as in combination.