Periparturient hypocalcemia is frequently observed and considered as a gateway disease that is associated with various health issues. The objective of this study was to evaluate the association of hypocalcemia with early-lactation milk yield, reproductive performance, and culling across a large number of different managerial systems. A prospective cohort study was conducted based on a convenience sample of 125 dairy herds from 8 federal states of Germany between February 2015 and August 2016. A blood sample was drawn from 1,709 animals within 48 h after parturition and analyzed for serum calcium concentration. After discarding cows (n = 283) with missing data, a total of 1,426 cows were considered for final analyses. The median time from calving to sampling was 14.0 h (interquartile range = 5.0-24.9 h). For each herd, a record of the herd management software was requested 150 d after the last cow was sampled. Serum calcium concentration of each cow was associated with early-lactation milk yield (Dairy Herd Improvement Association equivalent test 1 to 3), reproductive performance [days in milk (DIM) at first artificial insemination (AI), pregnancy at first AI, time to pregnancy within 150 DIM], and culling (until 60 DIM) data. Generalized linear mixed models were used to analyze continuous or categorical data. Shared frailty models were used for time to event data. Five different thresholds were used to define hypocalcemia. Thresholds ranged from 1.8 to 2.2 mmol/L using 0.1-mmol/L increments. Clinical hypocalcemia was defined as serum calcium concentration <2.0 mmol/L in combination with clinical signs (e.g., recumbency). The effect of hypocalcemia on milk yield was conditional on parity. In primiparous cows a serum calcium concentration <2.0 mmol/L (6.4% of cows were below this threshold) had no effect on milk production, whereas there was a tendency for multiparous cows with a serum calcium concentration <2.1 mmol/L (63.2% of cows were below this threshold) to produce 0.80 kg/d more milk compared with multiparous cows at or above the threshold. Multiparous cows suffering from clinical hypocalcemia produced 2.19 kg/d less milk compared with normocalcemic cows in early lactation. Calcium status was not associated with days to first insemination. Cows with a serum calcium concentration <1.9 mmol/L (34.6% of cows below this threshold) had decreased odds (odds ratio = 0.56) of pregnancy at first AI. A serum calcium concentration <1.8 mmol/L (24.1% of cows below this threshold) had a significant effect on time to pregnancy. Compared with animals with a serum calcium concentration ≥1.8 mmol/L, the hazard of becoming pregnant within 150 DIM was reduced when cows had a serum calcium concentration <1.8 mmol/L (hazard ratio = 0.68). Cows with a serum calcium concentration <2.0 mmol/L (44.3% of cows were below this threshold) had a 1.69 times greater hazard of being culled within the first 60 DIM compared with normocalcemic animals. The present study shows that the association of hypocalcemia with milk yield was conditional on parity and serum calcium concentration measured once within 48 h after calving. Considering reproductive performance and culling in early lactation, a negative effect of postpartum hypocalcemia was demonstrated.