This study is an investigation of risk factors and genetics of locomotion problems and subclinical mastitis (SCM) in Holstein cows. Risk factors of interest were related to the cow and herd management. Genetic parameters were estimated for locomotion and SCM with production and conformation traits. Two models for locomotion were explored to identify cow factors and management factors involved in the etiology of locomotion problems. The first model analyzed the association of first locomotion score (LS1) on second locomotion score (LS2). The second model analyzed cow and management risk factors for both LS1 and LS2 (locomotion score). Cow factors associated with LS2 and locomotion score were similar. Management factors associated with both LS2 and locomotion score were time of hoof trimming, alteration of the diet around calving, and bulk tank somatic cell count (BTSCC). Additional management factors associated with LS2 were formaldehyde and footbath usage. Locomotion score had a low heritability (0.06). Genetic correlations of locomotion score with body condition score and milk production were moderate. Locomotion score had moderate genetic correlations with udder related conformation traits and high genetic correlations with feet and leg traits. SCM was divided into three groups for analyses: SCM caused by major pathogens (MAS), SCM caused by major environmental pathogens (ENV), and SCM caused by major contagious pathogens (CONT). Genetic parameters for MAS were between parameters for ENV and CONT. Compared to ENV, MAS and CONT were associated with test day milk production (TD-milk) and test day somatic cell score (TD-SCS). CONT was also associated with the interaction of days in milk with TD-SCS. Cows raised in free-stalls were more likely to be infected with ENV. MAS, ENV, and CONT had low heritabilities of 0.011, 0.018, and 0.005, respectively. Phenotypic and genetic correlations between MAS and ENV and between MAS and CONT were high. Phenotypic and genetic correlations between ENV and CONT were small. TD-milk had a high positive genetic correlation with CONT. TD-SCS had a high positive genetic correlation with ENV. ENV and CONT had opposite genetic correlations with front udder attachment, front teat length, and front teat placement.