RATIONALE AND OBJECTIVES To provide reference data for computer-aided joint space analysis (CAJSA) based on a semiautomated and computer-aided diagnostic system for the measurement of joint space widths (ie, proximal-interphalangeal joint), considering gender-specific and age-related differences. MATERIALS AND METHODS A total of 869 subjects were enrolled (351 females/518 males) with radiographs of the hand. All participants underwent measurements of joint space distances at the proximal-interphalangeal articulation (JSD-PIP) of the second to fifth finger using CAJSA technology. RESULTS The data verify a notable age-related decrease of CAJSA parameters, showing an accentuated age-related joint space narrowing in women. Additionally, males showed a significant wider JSD-PIP (+15.4%) compared with the female cohort for all age groups. CONCLUSIONS Our data present gender-specific and age-related normative reference values for computer-aided joint space analysis of JSD-PIP and provide a valid and reliable quantification of disease-related joint space narrowing, particularly in patients with osteoarthritis and rheumatoid arthritis involving the peripheral small hand joints.