Laparoscopic surgery has become the standard for almost every surgical procedure; the benefits include faster recovery, less pain, and less risk of surgical site infection. Nonetheless, it demands technical knowledge and a high degree of experience from the surgical team to provide patients with the adequate treatment they need. Any variation of the normal anatomy, like situs inversus, can pose a challenge to the surgical team and will need more creativity to perform any surgery accurately and without complications. We present two situs inversus patients who needed surgical intervention due to cholelithiasis and acute appendicitis. After careful preoperative planning and modifications in the surgical technique, the patients underwent full recovery.