Background: Microsurgical free flap is widely used for the reconstruction of complex tissue defects, retrieval of anatomical structure, and improvement of function after debilitating injuries. Aim: Evaluate the effect of nursing teaching protocol on knowledge and postoperative complications for patients underwent microvascular free flap reconstruction of lower extremity. Patients and Methods: A quasi-experimental research design was used for a sample of 60 adult male and female patients, age ranged from 18-65 years old, underwent microvascular free flap reconstruction of lower extremity. They were randomly divided into 2 groups by flipping a coin [tails ꞊ control group (30 patients), heads꞊ intervention group (30 patients)]. Nursing teaching protocol was applied to the intervention group (teaching booklet) while control group received routine hospital care. Patients were followed up for 6 months in trauma department and microvascular reconstruction outpatient clinic. Tool (I): Patient assessment sheet and Tool II: Modified clavien–dindo classification. Results: Statistically significant difference between patients in intervention and control groups regarding patients' knowledge (p.value=0.001) and postoperative complications during follow up [after three weeks (P.value =0.02), three months (P.value =0.01), and six months (P.value =0.03)]. Improvement was obvious in intervention group than control group. Conclusion: Application of nursing teaching protocol showed obvious and significant effect in increasing patients' knowledge and reducing postoperative complications. Recommendation: To achieve the best patient outcomes, nurses must provide attentive nursing care for patients and nursing teaching booklet should be accessible in the microvascular unit for those patients.