We report the repair of a giant hiatal hernia by laparoscopic Collis gastroplasty and Nissen fundoplication in a patient with situs inversus totalis, highlighting the unique anatomic challenges in this case. The 52-year old female patient had Kartageners syndrome, a giant hiatal hernia, and a history of chronic severe gastroesophageal reflux disease with uncontrolled regurgitation. The laparoscopic procedure was accomplished with five ports placed in a mirror-image configuration, reversed from our standard positions. After visual confirmation of the complete reversal of the intraabdominal anatomy, we performed a modified Collis gastroplasty and Nissen fundoplication. Significant technical challenges were encountered intraoperatively. To the best of our knowledge, this report is the first of its kind in the literature. The use of advanced laparoscopic techniques is highly adaptable to unusual anatomy. Laparoscopic hiatal hernia surgery is feasible in patients with situs inversus.