There are currently several strategies for the treatment of symptomatic simple renal cysts, such as aspiration with sclerosants and laparoscopic deroofing. However, no clear indication exists for choosing between them. Here, we carried out a systematic review and a meta-analysis of studies, which compared symptomatic and radiological success between aspiration with sclerotherapy and laparoscopic deroofing. Results were reported as relative risk (RR) and 95% confidence interval (95% CI) using laparoscopic deroofing as control group. The symptomatic and radiological successes were evaluated by 6 and 3 studies, respectively. Notably, aspiration with sclerotherapy was associated with higher risk of failure than laparoscopic deroofing (RR = 2.82; 95% CI = 1.84–4.31 for symptomatic failure; RR = 8.31; 95% CI = 4.22–16.38 for radiological failure). On the other hand, however, aspiration with sclerotherapy was associated with less frequent complications, shorter treatment duration and post-treatment hospital stay, and lower costs. Thus, our work underlines benefits and drawbacks of each intervention, raising the need for further studies to design guidelines for the management of simple renal cysts.