Rectal lymphogranuloma venereum (LGV) has reemerged as a sexually transmitted infection among men who have sex with men (MSM), particularly those who are HIV-positive. We undertook a systematic review and meta-analysis to determine the efficacy of doxycycline (100 mg 2×/d for 21 days) for rectal LGV in MSM. Nine studies were included: 4 prospective, 4 retrospective, and 1 combined retrospective and prospective. In total, 282 MSM with rectal LGV were included in the studies. All studies reported using nucleic acid amplification tests to assess microbial cure. Most patients (>80%) had symptomatic rectal infection. The fixed-effects pooled efficacy for doxycycline was 98.5% (95% CI 96.3%–100%, I2 = 0%; p = 0.993). Doxycycline at 100 mg twice daily for 21 days demonstrated a high microbial cure rate. These data support doxycycline at this dosage and duration as first-line therapy for rectal LGV in MSM.