The identification of factors affecting longevity in dairy cows is of great importance to improve their length of productive life. Cows can be replaced for poor milk production (i.e. true productive lifespan, TPL) or other reasons than production (functional productive lifespan, FPL). The objective of the present study was to investigate the influence of milk yield, fat and protein contents, insemination status (INS), somatic cell count (SCC) and b-hydroxybutyrate (BHB) concentration in milk on TPL and FPL. Data included 70,748 Italian Holstein-Friesian cows that calved for the first time between 2014 and 2018. Proportional hazards models assuming a piecewise Weibull distribution of the baseline hazard function, with or without adjustment for milk production, were used to compute relative risks of culling associated with FPL and TPL, respectively. Our study revealed that milk yield, protein and fat contents, INS, SCC and concentration of BHB in milk exhibited significant relationships with TPL and FPL. In particular, the huge difference in risk ratios between high-and low-producing cows confirms the central role of milk production in culling decision-making. In addition, farmers appear more prone to cull cows with several events of high SCC and BHB concentration in milk. HIGHLIGHTS: Milk yield, fat and protein contents, insemination status, somatic cell count and ketosis affect productive lifespan in Italian Holstein cows. These factors, therefore, contribute significantly to culling decisions. The identified risk factors of culling can be exploited to improve the current management practices in Italian Holstein Friesian herds and cows' longevity.