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Although ciguatera fish poisoning (CFP) is the most common seafood intoxication worldwide, its burden has been difficult to establish because there are no biomarkers to diagnose human exposure.|We explored the incidence of CFP, percentage of CFP case-patients with laboratory-confirmed ciguatoxic meal remnants, cost of CFP illness, and potential risk factors for CFP.|During 2005 and again during 2006, we conducted a census of all occupied households on the island of Culebra, Puerto Rico, where locally caught fish are a staple food. We defined CFP case-patients as persons with gastrointestinal symptoms (abdominal pain, vomiting, diarrhea, or nausea) and neurological symptoms (extremity paresthesia, arthralgia, myalgia, malaise, pruritus, headache, dizziness, metallic taste, visual disturbance, circumoral paresthesia, temperature reversal, or toothache) or systemic symptoms (e.g., bradycardia) within 72 hr of eating fish during the previous year. Participants were asked to save fish remnants eaten by case-patients for ciguatoxin analysis at the Food and Drug Administration laboratory in Dauphin Island, Alabama (USA).|We surveyed 340 households during 2005 and 335 households during 2006. The estimated annual incidence of possible CFP was 4.0 per 1,000 person-years, and that of probable CFP was 7.5 per 1,000 person-years. One of three fish samples submitted by probable case-patients was positive for ciguatoxins. None of the case-patients required respiratory support. Households that typically consumed barracuda were more likely to report CFP (p = 0.02).|Our estimates, which are consistent with previous studies using similar case findings, contribute to the overall information available to support public health decision making about CFP prevention.