Background Cardiac arrest is a sudden and life-threatening event resulting in an end of cardiac activity, necessitating immediate intervention to prevent fatalities. In-hospital cardiac arrest (IHCA) presents a critical medical emergency, demanding swift and competent response. Cardiopulmonary resuscitation (CPR) is a key lifesaving intervention for IHCA, but the frequency of CPR events and the decay of CPR skills and knowledge among healthcare professionals (HCPs) raise concerns. Methods and Results In a prospective quasi-experimental study with no control group, 263 registered nurses (121 in critical care units and 144 in general care units) were assessed for CPR skills and knowledge retention at various time intervals. The result showed that overall decay after six months are almost the same for both groups. Knowledge decay started for both groups after one month and for both groups the highest level of decay was reported after three months, however the decay pattern was quite different. General units mean differences showed sudden sharp decline on three months which was not reported with critical care nurses who showed steady decay reaching to six months. Conclusions In this study, it is noteworthy that nurses in critical care units exhibited consistent decay in skills and knowledge, while those in general care units demonstrated a progressive decline over time.