To determine an association between magnesium (Mg) depletion and chondrocalcinosis, which has been reported but not investigated in a cross-sectional study. Prevalence of chondrocalcinosis was investigated in 144 individuals: 72 patients receiving home parenteral nutrition (HPN) compared with 72 age- and sex-matched controls. Presence of chondrocalcinosis was assessed by knee radiographs. Blood serum and globular Mg levels and 24-hour urinary Mg content were compared. Mean +/- SD age for both patients and controls was 51 +/- 17 years, and 51% in both groups were women. Mean duration of HPN was 6.4 years. Prevalence of chondrocalcinosis was markedly higher in patients receiving HPN than controls (16.6% versus 2.7%; P = 0.006, odds ratio [OR] 7.0, 95% confidence interval [95% CI] 1.45-66.1). Mean +/- SD serum and globular Mg levels were significantly lower in patients than controls (serum: 0.75 +/- 0.09 mmoles/liter versus 0.81 +/- 0.08 mmoles/liter, P = 0.0006; globular Mg: 1.8 +/- 0.31 mmoles/liter versus 2.0 +/- 0.35 mmoles/liter, P = 0.0003). Twenty-four-hour urinary Mg level was lower in patients than controls (mean +/- SD 3.85 +/- 1.50 mmoles versus 5.37 +/- 3.71 mmoles; P = 0.001). Prevalence of chondrocalcinosis was significantly higher in patients with a low serum Mg level (OR 13.5, 95% CI 2.76-127.3, P < 0.0001), with a similarly high but not significant occurrence of chondrocalcinosis in patients with a low globular Mg level (OR 4.09, 95% CI 0.603-20.26, P = 0.08) and in patients with a low 24-hour urinary Mg level (OR 3.9, 95% CI 0.77-16.34, P = 0.05). Long-lasting Mg depletion is strongly associated with chondrocalcinosis.