Background: The duration of use of oxymetazoline hydrochloride nasal spray is limited due to the risk of rhinitis medicamentosa or rebound congestion. In the United States, there is a 3-day limit on duration of use mandated by the FDA OTC Drug Monograph, whereas in some countries in Europe, the limit is 7 days. Design: Single center, double-blind, randomized, placebo-controlled, parallel group study in otherwise healthy adults, experiencing nasal congestion. Objectives: The primary objective of this study was to determine whether rebound congestion occurs after 7 days of treatment with twice daily dosing using 1 of 4 doses of oxymetazoline Hydrochloride nasal spray or saline control. The secondary objective was to determine and compare the nasal decongestant dose response of the 4 dosages of oxymetazoline hydrochloride nasal spray. Population: One hundred forty-three (143) subjects enrolled in the study, 139 completed the study and 138 included in the efficacy analysis. Methods: Subjects were randomized to one of five groups: 0.025% Oxymetazoline Hydrochloride, one 50 µL spray per nostril. 0.025% Oxymetazoline Hydrochloride, one 100 µL spray per nostril. 0.05% Oxymetazoline Hydrochloride HCl, two 50 µL sprays per nostril. 0.05% Oxymetazoline Hydrochloride HCl, two 100 µL sprays per nostril. Saline control, two 100 µL sprays per nostril. All subjects administered the assigned spray twice daily, for seven days. Efficacy evaluations were performed on Days 1, 4, 7, and 8 (12-24 hours post-treatment discontinuation). The degree of nasal congestion (primary efficacy variable) was rated on a 100 mm visual analog scale (VAS100mm). Results: Comparison of congestion scores (VAS100mm) at baseline with scores at Day 1, 4 and 7 of continuous treatment and at Day 8 (12-16 hours post treatment discontinuation) showed lack of subjective rebound congestion at each timepoint. The mean AUCs (difference in baseline congestion score) for the two highest doses of oxymetazoline hydrochloride (0.05%, 50 µL and 100 µL) were significantly greater than that of saline, whereas the mean AUCs for the two lowest doses (0.025% 50 µL and 100 µL) were not, indicating a dose response effect. Conclusion: Patients did not experience rebound congestion after using oxymetazoline hydrochloride at any of the evaluated doses, with twice daily application, for seven consecutive days and 12-24 hours following treatment discontinuation. There was a trend towards a dose response effect for oxymetazoline hydrochloride nasal spray.