Background and aims Pain management is one of the most important responsibilities of nurses in an intensive care unit (ICU). It is difficult to perform pain assessment appropriately in patients who are unable to report their pain. This study is aimed to determine the impact of implementing the critical care pain observation tool (CPOT) on the amount and frequency of analgesics' administration in ICUs. Materials and methods This interventional study was conducted in 2014. Sixty nurses and 240 patients were studied. This study was carried out in three phases: first the data about amount and frequency of analgesic administration were extracted from patients' medical files. Then the CPOT was implemented into the nursing assessment process and finally, nurses' performance regarding the amount and frequency of analgesic administration was recorded. This data obtained before and after intervention were analyzed using chi-square and independent t-test p values less than 0.05 were considered significant. Results In this interventional study, we found that there was no difference in the demography and cause of ICU admission before and after implementation of CPOT (age p = 0.937, gender p = 0.996, and the cause of admission p = 0.996). We found that after implementing the CPOT into the nursing assessment process, the amount of analgesics administered (7.95 ± 8.77 mg vs. 11.01 ± 11.04 mg, p = 0.018) and the frequency of administration (2.91 ± 1.38 vs. 4.16 ± 0.99, p <0.001) increased significantly. Moreover, there was a significant increase in the frequency of pain assessment per patient per day in nursing practice after implementation of CPOT as compared to the practice before (7.2 ± 2.48 vs. 1.03 ± 1.63, p <0.001). The mean pain scores before and after the intervention (5.5 ± 1.08 vs.2.2 ± 0.48) were also significantly different. Conclusion Applying CPOT, as an objective mean of pain assessment, was effective in improving the performance of ICU nurses in assessment and management of patients' pain. It increased the amount and frequency of analgesic administration. We can recommend that COPT is a useful tool for assessment and management of pain in ICU patients and should be implemented in all ICUs. How to cite this article Modanloo M, Mohsenpour A, et al. Impact of Implementing the Critical Care Pain Observation Tool on Nurses' Performance in Assessing and Managing Pain in the Critically Ill Patients. Indian J Crit Care Med 2019;23(4):165-169.