The aim of the study was to examine the relationship between comorbidities and pain, physical function and health-related quality of life (HRQoL) after total hip arthroplasty (THA) and total knee arthroplasty (TKA). A cross-sectional retrospective survey was conducted including 19 specific comorbidities, administered in patients who underwent THA or TKA in the previous 7-22 months in one of 4 hospitals. Outcome measures included pain, physical functioning, and HRQoL. Of the 521 patients (281 THA and 240 TKA) included, 449 (86 %) had ≥1 comorbidities. The most frequently reported comorbidities (>15 %) were severe back pain; neck/shoulder pain; elbow, wrist or hand pain; hypertension; incontinence of urine; hearing impairment; vision impairment; and cancer. Only the prevalence of cancer was significantly different between THA (n = 38; 14 %) and TKA (n = 52; 22 %) (p = 0.01). The associations between a higher number of comorbidities and worse outcomes were stronger in THA than in TKA. In multivariate analyses including all comorbidities with a prevalence of >5 %, in THA dizziness in combination with falling and severe back pain, and in TKA dizziness in combination with falling, vision impairments, and elbow, wrist or hand pain was associated with worse outcomes in most of the analyses. A broad range of specific comorbidities needs to be taken into account with the interpretation of patients' health status after THA and TKA. More research including the ascertainment of comorbidities preoperatively is needed, but it is conceivable that in particular, the presence of dizziness with falling, pain in other joints, and vision impairments should be assessed and treated in order to decrease the chance of an unfavorable outcome.