Improvement in patient daily functioning and well-being resulting from disease-related symptom relief is increasingly viewed as a clinically relevant therapeutic outcome. The objective of this study was to evaluate the health-related quality of life (HRQL) effects, safety and efficacy of cetirizine in the treatment of seasonal allergic rhinitis, and impact on self-reported work/school-related productivity and activity impairment (WPAI). This was a double-blind, placebo-controlled, parallel-group study. Adult patients (n = 865) were randomized to daily treatment for 2 weeks with cetirizine or placebo. Patient disease-specific HRQL and WPAI were assessed at baseline and weeks 1 and 2 of treatment using the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and Allergy-Specific Work Productivity and Activity Impairment (WPAI-AS) Instrument, respectively. Treatment with cetirizine resulted in greater (p < 0.001) improvement in overall RQLQ and individual domain scores (activities, sleep, non-nose/eye symptoms, practical problems, nasal symptoms, eye symptoms, emotional), as compared with placebo. Cetirizine therapy produced a 28.9% mean reduction in total symptom severity complex (TSSC) score versus 12.7% with placebo at study end. Work/school productivity and activity impairment were significantly (p < 0.001) decreased from baseline for cetirizine-treated patients compared with placebo. The incidence of treatment-related side effects was similar between groups. Cetirizine provides safe and effective symptomatic relief in adults with SAR while significantly improving HRQL and providing a positive impact on work/school-related productivity and activity impairment. These results provide a more comprehensive assessment of cetirizine, indicating that its benefits extend beyond conventional measures of clinical outcome.