Hairy cell leukemia is an uncommon chronic B-cell lymphoproliferative disorder. Various treatment options are available. The objective of the study was to evaluate through meta-analysis the pooled proportions of patients responding to each therapeutic agent. We conducted a systematic review and meta-analysis to estimate the pooled response rate to modern hairy cell leukemia therapies. Articles published between January 1992 and August 2017 were identified by searching PubMed, Web of Science, and the Cochrane Library. Weighted meta-analysis of proportion using a random-effects model was performed for each treatment option. Of 3287 articles viewed, 20 articles describing 21 studies were included in the meta-analysis. The pooled random effect of the response rate was up to 99% in both cladribine with rituximab at 0.99 (95% confidence interval [CI], 0.98-1.0) and vemurafenib treatment at 0.99 (95% CI, 0.95-1.0). The pooled random effect of the complete response rate was up to 97% (0.97; 95% CI, 0.88-1.0) in cladribine followed by rituximab. The most effective therapy in patients treatment naïve and in first relapse was cladribine with rituximab maintenance.