Background: There are different surgical techniques used for thymectomy. Each technique has its own advantages and disadvantages. However, using a less invasive approach would provide a better outcome. Methods: From June 2015 to February 2017, a prospective study included a total number of 50 patients of non-thymomatous myasthenia gravis (MG) who were randomly divided into two groups: group A (25 patients who underwent VATS thymectomy), and group B (25 patients who underwent thymectomy via ministernotomy). Efficacy and outcome of both procedures were compared. Patients were followed-up for at least one year postoperatively. Results: Both procedures were safe and effective in the management of MG. There was no significant difference between both groups regarding preoperative data. In VATS group, there were significant decreased operative times (p value ¼ 0.00), significant decreased blood loss (p value ¼ 0.039), significant decreased postoperative respiratory and cardiac complications (p value ¼ 0.025 and 0.018 respectively) and significant shorter length of ICU and hospital stays (p value ¼ 0.039 and 0.007 respectively) when compared to ministernotomy group. There was no statistically significant difference between both groups regarding complete stable remissions and clinical improvement. No mortality was recorded in both groups. Conclusions: Thoracoscopic thymectomy should be the technique of choice in the management of MG. It has better intraoperative and short-term results than that of thymectomy via ministernotomy. However, longer periods of follow-up is needed to evaluate long-term results properly.