Although laparoscopic fenestration has become an established treatment in symptomatic liver cyst patients in the recent years, the success of surgical treatment cannot only be evaluated by post-operative morbidity and mortality. Therefore, the aim of this study was to analyze the safety of laparoscopic fenestration of non-parasitic liver cysts and to assess the impact of this therapy on patients' quality of life. A total of 43 patients who underwent laparoscopic fenestration of non-parasitic liver cysts at our center were included in this study. Post-operative course was assessed and patients' quality of life was evaluated before surgery and at present time using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ C-30). The results were that, post-operative morbidity and mortality rates were 0%. After a median follow-up of 49 months (19-97 months) the recurrence rate was 11.1% for simple liver cysts (SLC) and 42.9% for polycystic liver disease (PCLD). Thirty-one out of 43 patients (72.1%) completed the EORTC C-30 questionnaire. There was highly significant post-operative improvement in global health status (p < 0.001) as well as in physical (p = 0.002), role (p = 0.004), emotional (p = 0.003) and social (p = 0.001) functioning. Furthermore, a significant reduction of symptoms could be shown for pain (p < 0.001), nausea and vomiting (p = 0.001), appetite loss (p = 0.006), insomnia (p = 0.04) and fatigue (p = 0.025). To conclude, laparoscopic fenestration of symptomatic non-parasitic liver cysts is a safe procedure with good long-term results and the patients' benefit of this intervention is excellent as shown by highly significant improvement in patients' quality of life.