Objectives/HypothesisTo evaluate the efficacy and safety of a slow‐release form of bepotastine salicylate (HL151, Belion CR) in patients with perennial allergic rhinitis (PAR).Study DesignDouble‐blind, placebo‐controlled multicenter comparative study.MethodsTwo hundred seventy‐two PAR patients (aged 19–65 years) were studied to determine the efficacy and safety of HL151 (20 mg once daily administration) relative to those of a placebo in terms of improvements in total and nasal symptom scores. The subjects were randomized to the placebo (n = 138) or HL151 group (n = 134, 20 mg orally once daily for 4 weeks), and reflective and instantaneous total nasal symptom scores (TNSS) were measured daily in comparison with baseline. Among 272 subjects, 229 subjects (119 in the placebo group, 110 in the HL151 group) who completed the study were included for efficacy analysis.ResultsInstantaneous and reflective TNSS and nasal symptoms such as rhinorrhea, nasal itching, and sneezing at 2 and 4 weeks showed that HL151 was superior to the placebo (all P < .05). There were no significant differences in terms of adverse events and adverse drug reactions between the two groups. Regarding serious adverse events, there was only one case of acute hepatitis B, which was reported not to be associated with HL151.ConclusionsThis multicenter trial showed that once‐daily use of HL151 is efficacious and safe in adult patients with PAR and could improve compliance due to its convenience.Level of Evidence1b Laryngoscope, 131:E702–E709, 2021