The aim of this study was to investigate factors associated with mucosal pain in patients with partial removable dental prostheses (PRDPs). In this hospital-based cross-sectional study, 333 patients wearing 500 PRDPs (mean age 71·4 years, men 33·3%) were consecutively recruited from prosthetic clinic of a dental hospital in Japan. Subjects rated pain intensity and frequency of denture-bearing mucosa. An examiner recorded age, gender and systemic diseases as well as dental, mucosa, denture, sensory, behavioural- and psychological-related characteristics that were possibly associated with the mucosal pain. Multivariate analyses were performed to analyse factors related to mucosal pain. Pain intensity was rated as more than score 0 (presence) in 34·2% (171/500) PRDPs, and pain was experienced after denture delivery in 42·8% (214/500) PRDPs. Logistic regression analyses showed that younger age, mucosal damage, poor mucosal condition, bone prominence, poor residual ridge, higher pain sensitivity, presence of awake bruxism, perception of oral dryness, interim denture wear and high number of missing teeth were significant independent predictors for the presence of the mucosal pain intensity and/or frequency (P < 0·05). Multiple factors are associated with mucosal pain in patients with PRDPs. Oral mucosal characteristics, age, pain sensitivity and behavioural factors seem to be more critical for mucosal pain than distribution of missing teeth and number of abutment teeth.