We present a large review of 446 cases of paracentric inversions (PAI), including 120 new cases, to assess their incidence, distribution, inheritance, modes of ascertainment, interchromosomal effects, viable recombinant offspring, and clinical relevance. All 23 autosomes and sex chromosomes had inversions. However, none were identified in chromosome arms 18p, 19q, 20q, and Yp. PAI were most commonly reported in chromosomes 1, 3, 5, 6, 7, 11, and 14 and less frequently in chromosomes 4, 16, 17, 18, 19, 20, 21, 22, and Y. Inversions were most common in chromosome arms 6p, 7q, 11q, and 14q and observed least in chromosome arms 2p, 2q, 3q, 4q, and 6q. Frequently encountered breakpoints included 3(p13p25), 6(p12p23), 6(p12p25), 7(q11q22), and 11(q21q23). Ascertainment was primarily incidental (54.5%), mental retardation and/or congenital anomalies (22.2%), spontaneous abortions (11.4%), associations with syndromes (3.0%), and infertility (2.0%) accounted for the remainder. Ascertainment was neither related to the length of the inverted segment nor to specific inversions except for PAI of Xq which often presented with manifestations of Ullrich-Turner syndrome. Sixty-six percent of PAI were inherited while 8.5% were de novo. Recombination was observed in 17 cases, 15 of which resulted in a monocentric chromosomal deletion or duplication. No common factors were identified that suggested a tendency towards recombination. The incidence of viable recombinants was estimated to be 3.8%. This review documents that PAI are perhaps more commonly identified than suggested in previous reviews. Despite the possible bias of ascertainment in some cases, there may be associated risks with PAI that require further examination. Our data suggest that PAI carriers do not appear to be free of risks of abnormalities or abnormal progeny and caution is recommended when counseling.