The present study analysed the importance of individual variables and different thematic blocks of production areas, management, and herd infectious disease status on cow persistence, characterised by herd on-farm mortality rate (MR), culling rate (CR), and mean age of culled cows (MAofCC) applying multiblock partial least squares (mbPLS) analysis. This study included 120 free-stall dairy herds with ≥ 100 cows. Data on the previous year’s predominant cow housing system and management practices were collected, and on-farm measurements and cow scoring were performed. Bulk tank milk (BTM) and heifer blood samples (10 samples per herd) were collected and analysed for antibodies against the selected pathogens. In total, 172 variables were aggregated into 14 thematic blocks. The annual CR, MR, and MAofCC values were calculated for each herd. Thematic blocks with significant impact on cow persistence (included herd MR, CR and MAofCC) were ‘infectious diseases’ (block importance index out of all blocks = 13.6%, 95% CI 10.3; 20.5), ‘fertility management’ (16.3%, 95% CI 6.8; 26.9), ‘lactating cow management’ (11.5%, 95% CI 6.4; 17.8), ‘milking’ (11.3%, 95% CI 3.2; 17.1), ‘herd characteristics’ (10.1%, 95% CI 6.3; 14.2), ‘close-up period management’ (9.7%, 95% CI 2.7; 15.7), ‘calving management’ (7.9%, 95% CI 3.1; 11.4) and ‘disease management’ (7.3%, 95% CI 0.2; 12.0). Variable categories with the highest importance in explaining composite outcome including herd MR, CR and MAofCC were rear-end and udder lesions in ≥ 20% of the cows, BTM and heifers seropositive to bovine respiratory syncytial virus, vaccination against bovine herpesvirus 1, twice daily milking and herd location in Northwest region. Larger herd size, higher levels of milk yield, and rearing predominantly Holstein breed cattle were herd factors associated with poorer cow persistency. Grazing cows and having semi-insulated barns were associated with lower CR and MR, respectively. Heat detection and farm pregnancy testing strategies were significant factors in the fertility block. Using disposable dry papers for teat cleaning and not using any wet teat-cleaning tools were risk factors for high MR. A robotic milking system was protective for increased herd MR and CR. A high pre-calving body condition score and poor rear body cleanliness of ≥ 30% of cows were associated with inferior herd persistency outcomes. Calving in group pens with deep litter bedding was associated with a lower CR. Multiblock PLS model is innovative tool that helped to identify most influential farming areas but also single risk factors associated with cow persistency described by multiple parameters.