Abstract Background Manual handling operations (MHO) are known to be risk factors for work-related upper limb disorders (WRULDs), e.g. symptoms and conditions such as carpal tunnel syndrome. To estimate the risk of WRULDs, a Key Indicator Method (KIM) for the risk assessment of MHO was developed. The method was validated in regard to different criteria, including face validity, criterion validity, reliability and further aspects concerning utility. This paper describes the KIM-MHO and criterion validity of this method with reference to prevalence of musculoskeletal disorders (MSDs). Methods A cross-sectional sample of 643 employees exposed to MHO was compared to a reference group of 804 unexposed subjects predominantly working at visual display terminals. The Nordic Questionnaire and a standardized clinical examination were used to obtain the 7-day and 12-months prevalence of symptoms and clinical conditions of the musculoskeletal system. Job specific exposure levels to MHO were assessed by ergonomists using the KIM-MHO. The resulting risk scores were categorized into risk categories 1 - low risk (reference group), 2 - increased risk, 3 - highly increased risk, and 4 - high risk. Log-linear Poisson regression models were applied to obtain adjusted prevalence ratios (PR) with 95%-confidence intervals. Results The 7-day prevalence of symptoms for subjects in risk category 3 compared to risk category 1 was significant for the regions shoulder [women (w): PR 1.8 (1.2–2.7), men (m): PR 2.3 (1.2–4.4)], elbow [w: PR 3.3 (1.5–7.2), m: PR 2.4 (0.8–7.3)], and hand/wrist [w: PR 3.0 (1.7–5.3), m: PR 5.5 (2.7–11.3)]. The 7-day prevalence of symptoms for risk category 4 was also significant for the regions shoulder [w: PR 1.9 (1.3–2.8), m: PR 1.9 (1.3–2.7)], elbow [w: PR 4.5 (2.3–8.7), m: PR 3.3 (2.1–5.4)], and hand/wrist [w: PR 4.2 (2.6–6.9), m: PR 5.5 (3.5–8.5)]. The 12-months prevalence in these joint regions show comparable increases in the risk categories 3 and 4. Conclusions The KIM-MHO is valid in regard to criterion validity. The hypothesis could be confirmed, that high risk scores were associated with an increased prevalence of symptoms and clinical conditions especially in the shoulder, elbow and hand/wrist regions among employees exposed to MHO.