Andes virus (ANDV) infection, which has a case fatality rate of 37% in Chile, often occurs in household clusters and may be transmitted from person to person.To determine the incidence and risk factors for additional household cases, we conducted a prospective study among recent household contacts of persons with hantavirus cardiopulmonary syndrome (HCPS) in Chile, including testing of serum for anti-hantavirus antibodies and blood cells for ANDV RNA by reverse-transcription polymerase chain reaction (RT-PCR).We enrolled 76 index case patients and 476 household contacts, of whom 16 (3.4%) developed HCPS; 32.6% of 92 cases occurred in household clusters. The risk of HCPS was 17.6% among sex partners of index case patients, versus 1.2% among other household contacts (P<.001). Person-to-person transmission was definite in 3, probable in 9, and possible in 2 of the 16 additional household case patients. We detected ANDV RNA by RT-PCR in peripheral blood cells 5-15 days before the onset of symptoms or the appearance of anti-hantavirus antibodies.In recent household contacts of persons with HCPS in Chile, the risk of HCPS was greatest among sex partners. Among the household contacts who developed HCPS, viremia preceded the onset of symptoms and the appearance of anti-hantavirus antibodies by up to 2 weeks.