Objective <p>The aim of this prospective study is to evaluate the efficacy and safety of sublingual immunotherapy (SLIT) in moderate to severe monosensitized and polysensitized allergic rhinitis patients.</p> Methods <p>In this study,75 patients with moderate to severe allergic rhinitis were randomized to receive SLIT (<i>n</i> = 50) or placebo (<i>n</i> = 25) for 1-year duration. Subjective and objective evaluations were performed at baseline and then at 6 and 12 months of therapy. Allergen-specific IgG and nasal smear for eosinophilic count were studied at baseline and 12 months.</p> Results <p>SLIT demonstrated a significant reduction of total nasal symptom scores (TNSS), Juniper Rhinitis Quality of Life Questionnaire (RQLQ) scores, total medication score (TMS), and visual analogue scale score (VAS) (<i>P</i> &lt; .001) when compared with placebo. Serum sIgG levels increased in the SLIT group at 12 months compared with placebo group (<i>P</i> &lt; .001). Nasal smear for eosinophilic count decreased in SLIT group at 12 months. No relevant systemic symptoms were registered.</p> Conclusion <p>SLIT is an effective, safe, and well-tolerated treatment for allergic rhinitis.</p>