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Aims: To compare the efficacy and tolerability of Oxymetazoline 0.05 % plus Dexpanthanol 5% versus Xylometazoline 0.1% nasal drops in patients with nasal congestion due to allergic rhinitis and following nasal surgery. Methods: An investigator-blind, randomized, controlled, phase IV clinical trial conducted in 100 patients with acute allergic rhinitis or patients post-nasal surgery. Patients received either Oxymetazoline 0.05% with Dexpanthanol 5% (OD) or Xylometazoline 0.1% (XO) nasal drops. Results: Relief from nasal congestion was significantly better in the OD group then in the XO group (mean nasal scores 1.24 vs 1.86). Significantly more improvement in sneezing and decrease in nasal discharge was seen in the OD group than the XO group. Nasal irritation in the OD group was significantly less as compared to XO group (0.38 v/s 1.12 on second day and 0.10 vs 0.36 on the fourth day). The recovery time for OD group was 1,08 hours, which was significantly (46 min) lesser than that of the XO group. Rebound congestion was significantly less in OD as compared to XO group (6.25% vs 82.98%). 93.75% of the physicians in the OD group and 51.28% in XO group reported response to therapy as good to excellent. 95.83% patients in the OD group and only 52.91% patients in the XO group rated tolerability to therapy as good to excellent. Conclusion: Oxymetazoline and dexpanthenol combination has a better efficacy, shorter recovery time, causes lesser rebound congestion and has better tolerability than xylometazoline. [ABSTRACT FROM AUTHOR]