Aims: Iatrogenic cardiac perforation is an uncommon but potentially fatal complication of invasive cardiac procedures. When non-surgical management fails, urgent cardiac surgery is required. Standard surgical approach is usually through full sternotomy. However, we propose a less invasive and equally effective technique with video-assisted thoracoscopic surgery (VATS). Methods: This single-center retrospective study in a tertiary hospital identified all patients requiring surgical intervention due to iatrogenic cardiac perforation over a period of 5 years. Patients were grouped by surgical approach, being either sternotomy or VATS. Primary endpoints were length of ICU stay, hospital stay, 30-day mortality and all round mortality. Results: 25 patients were identified: 11 in the sternotomy-group and 14 in the VATS-group. Preoperative baseline characteristics were equal. Significant difference was found for 30-day mortality (p < 0.05). There was no difference for the other endpoints. Conclusions: Video-assisted thoracoscopic surgery is a promising alternative to standard sternotomy for iatrogenic cardiac perforations after invasive cardiac procedures.