BACKGROUND: Persistent symptoms, mainly joint and muscular pain and depression, have been reported several months after Chikungunya virus (CHIKV) infection. Their frequency and their impact on quality of life have not been compared with those of an unexposed population. In the present study, we aimed to describe the frequency of prolonged clinical manifestations of CHIKV infection and to measure the impact on quality of life and health care consumption in comparison with that of an unexposed population, more than one year after infection. METHODOLOGY/PRINCIPAL FINDINGS: In a retrospective cohort study, 199 subjects who had serologically confirmed CHIKV infection (CHIK+) were compared with 199 sero-negative subjects (CHIK-) matched for age, gender and area of residence in La Réunion Island. Following an average time of 17 months from the acute phase of infection, participants were interviewed by telephone about current symptoms, medical consumption during the last 12 months and quality of life assessed by the 12-items Short-Form Health Survey (SF-12) scale. At the time of study, 112 (56%) CHIK+ persons reported they were fully recovered. CHIK+ complained more frequently than CHIK- of arthralgia (relative risk = 1.9; 95% confidence interval: 1.6-2.2), myalgia (1.9; 1.5-2.3), fatigue (2.3; 1.8-3), depression (2.5; 1.5-4.1) and hair loss (3.8; 1.9-7.6). There was no significant difference between CHIK+ and CHIK- subjects regarding medical consumption in the past year. The mean (SD) score of the SF-12 Physical Component Summary was 46.4 (10.8) in CHIK+ versus 49.1 (9.3) in CHIK- (p = 0.04). There was no significant difference between the two groups for the Mental Component Summary. CONCLUSIONS/SIGNIFICANCE: More than one year following the acute phase of infection, CHIK+ subjects reported more disabilities than those who were CHIK-. These persistent disabilities, however, have no significant influence on medical consumption, and the impact on quality of life is moderate.