Abstract OBJECTIVE To investigate risk factors, clinical features, and prognostic indicators in guinea pigs with urolithiasis. ANIMALS 158 guinea pigs with urolithiasis. PROCEDURES Medical records of an exotics animal specialty service were searched, identifying guinea pigs with urolithiasis. Signalment, clinical data, and outcomes were recorded. Variables of interest were analyzed for statistical associations with outcome. RESULTS Overall, 54.4% (86/158) of animals survived to discharge. Median survival time was 177 days. Females (53.2%; 84/158) were more common than males (46.8%; 74/158). Males were presented younger (mean age, 3.64 years) than females (4.41 years). In 81 of 154 (52.5%) cases, animals were presented with primary urinary concerns, while 73 (47.5%) presented for nonurinary primary concerns. Females more commonly presented with distal urinary tract urolithiasis (63/84; 75%) but fared better overall with a longer median survival time (1,149 days) than males (59 days). Surgical intervention was not a risk factor for nonsurvival; however, increased age (> 4.1 years), male sex, anorexia, weight loss, and lower rectal temperature (< 37.2 °C) on presentation were associated with nonsurvival. Reoccurrence was noted in 13.9% (22/158) of cases, at an average of 284 days. CLINICAL RELEVANCE Urolithiasis should always be considered a differential diagnosis for any unwell guinea pig. In particular, distal urinary tract urolithiasis should be considered in females. A poorer prognosis was associated with older, male guinea pigs, and those displaying anorexia, weight loss, and hypothermia. The need for surgical intervention should not confer a poorer outcome. Further studies are needed to determine specific risk factors and identify possible preventative measures.