Background: Single-port robotic-assisted radical prostatectomy has been reported as a safe and feasible technique. However, recent studies comparing single-port versus multiple-port robotic radical prostatectomy have displayed conflicting results. Objectives: To investigate the benefit of single-port robotic radical prostatectomy and the impact on outcome compared to multiple-port robotic radical prostatectomy. Methods: Based on PRISMA and AMSTAR criteria, a systematic review and meta-analysis were carried out. Finally, we considered the controlled studies with two cohorts (one cohort for single-port RARP and the other cohort for multiple-port RARP). For statistical analysis, Review Manager (RevMan) software version 5.4 was used. The Newcastle-Ottawa Scale was employed to assess the risk of bias. Results: Five non-randomized controlled studies with 666 patients were included. Single-port robotic radical prostatectomy was associated with shorter hospital stays. Only 60.6% of single-port patients (109/180) required analgesia compared to 90% (224/249) of multiple-port patients (Z = 3.50; p = 0.0005; 95% CI 0.07:0.47). Opioid administration was also significantly lower in single-port patients, 26.2% (34/130) vs. 56.6% (77/136) (Z = 4.90; p < 0.00001; 95% CI 0.15:–0.44) There was no significant difference in operative time, blood loss, complication rate, positive surgical margin rate, or continence at day 90. Conclusion: The available data on single-port robotic radical prostatectomy is very limited. However, it seems comparable to the multiple-port platform in terms of short-term outcomes when performed with expert surgeons. Single-port prostatectomies might provide a shorter hospital stay and a lower requirement for opioids; however, randomized trials with long-term follow-up are mandatory for valid comparisons.