We performed a comprehensive systematic review and network meta-analysis (NMA) to assess the efficacy of pharmacological agents for the treatment of proliferative vitreoretinopathy (PVR) following retinal detachment (RD) surgery. A systematic search was performed across PubMed, Scopus, Web of Science, and Embase. Randomized and non-randomized controlled trials and comparative observational studies evaluating the effect of pharmacological agents in a clinical setting were included. The primary outcome was retinal reattachment rate, and secondary outcomes were PVR recurrence, reoperation, intraocular pressure (IOP), epiretinal membrane (ERM), and macular edema. A total of 23 studies with 1749 eyes were included. Twelve different drugs or drug combinations were assessed. The NMA was performed for retinal reattachment, PVR recurrence, and reoperation rate outcomes. Among the pharmacological agents analyzed, adjunctive therapy with 13-cis-retinoic acid (13-cis-RA) demonstrated a statistically significant improvement in retinal reattachment rates (RR=1.36, 95 % CI: 1-1.84) and a reduction in reoperation rates (RR=0.23, 95 % CI: 0.07-0.69) compared to the control group, while none of the other drugs had statistically significant results. Additionally, adjunctive therapy did not yield significant improvements in IOP, ERM, or macular edema, except for a reduction in macular edema associated with dexamethasone in one study. This systematic review and NMA indicate that most pharmacological agents could not significantly improve retinal reattachment, reduce PVR recurrence, or lower reoperation rates following RD surgery. 13-cis-RA was the only drug that showed a significant impact on lowering retinal detachment and reoperation rates. Further high-quality clinical trials are warranted to confirm these findings.