Objective: To study the effect of comfortable operating room nursing on postoperative analgesia and nursing satisfaction in patients with femoral nerve block and self-controlled analgesia. Methods: A case-control study protocol was designed. During the implementation of the protocol, a total of 42 patients who underwent artificial knee replacement surgery were included and randomly divided into 2 groups. All patients underwent femoral nerve block anesthesia combined with self-controlled analgesia. In the operating room care, the control group was given routine care, and the observation group was given comfort care, including personalized health education, posture care, psychological care, environmental and temperature care. Patients’ postoperative analgesic effect [evaluated by Visual Analogue Scale (VAS)] and nursing satisfaction [adopted by the “Nursing Satisfaction Questionnaire” survey] were used as the main observation indicators of this study. Results: At 4, 8, 12, and 24 h after surgery, the average VAS score in the observation group was lower than that in the control group (P<0.05). Nursing satisfaction of the observation group was higher than that of the control group (95.24% vs 76.19%, P<0.05). Conclusion: The application of comfortable nursing in the operating room nursing of patients with femoral nerve block combined with self-controlled analgesia can effectively improve the postoperative analgesic effect and nursing satisfaction.