Epidemic cholera reached Guatemala in July 1991. By mid-1993, Guatemala ranked third in the hemisphere in reported cases of cholera. We conducted a case-control study with two age-, sex-, and neighbourhood-matched controls per patient in periurban Guatemala City. Twenty-six patients hospitalized for cholera and 52 controls were enrolled. Seven (47%) of 15 stool cultures obtained after admission yielded toxigenic Vibrio cholerae Ol. All seven were resistant to furazolidone, sulfisoxazole, and streptomycin, and differed substantially by pulsed-field gel electrophoresis from the Latin American epidemic strain dominant in the hemisphere since 1991. In univariate analysis, illness was associated with consumption of left-over rice (odds ratio [OR] = 7·0, 95% confidence interval [CI] = 1·4–36), flavored ices (‘helados’) (OR = 3·6, CI = 1·1–12), and street-vended non-carbonated beverages (OR = 3·8, CI = 1·2–12) and food items (OR = 11·0, CI = 2·3–54). Street-vended food items remained significantly associated with illness in multivariate analysis (OR = 6·5, CI = 1·4–31). Illness was not associated with drinking municipal tap water. Maintaining water safety is important, but slowing the epidemic in Guatemala City and elsewhere may also require improvement in street vendor food handling and hygiene.