Introduction: After an endoscopic third ventriculostomy (ETV) fails, it is unclear how well subsequent treatment fares, especially in comparison to shunts inserted as primary treatment. In this study, we present a further analysis of the infants enrolled a prospective multicentre study who failed ETV and describe the outcome of their subsequent treatment, comparing this to those who received shunt as their primary treatment. Methods: This was a post hoc analysis of data from the International Infant Hydrocephalus Study (IIHS)—a prospective, multicentre study of infants with hydrocephalus from aqueductal stenosis who received either an ETV or shunt. In the current analysis, we compared the results of the 38 infants who failed ETV and the 43 infants who received primary shunt. Patients were followed prospectively for time to treatment failure, defined as the need for repeat CSF diversion procedure (shunt or ETV) or death due to hydrocephalus. Results: There were a total of 81 patients: 43 primary shunts, 34 shunt post-ETV, and 4 repeat ETV. The median time between the primary ETV and the second intervention was 29 days (IQR 14–69), with no significant difference between repeat ETV and shunt post-ETV. Median length of available follow-up was 800 days (IQR 266–1651), during which time, failure was noted in 3 (75.0%) repeat ETV patients, 10 (29.4%) shunt post-ETV patients, and 9 (20.9%) primary shunt patients. In an adjusted Cox regression model, the risk of failure was higher for repeat ETV compared to primary shunt, but there was no significant difference between primary shunt and shunt post-ETV. No other variable showed statistical significance. Conclusions: In our prospective study of infants with aqueductal stenosis, there was no significant difference in failure outcome of shunts inserted after a failed ETV and primary shunts. Therefore, our data do not support the notion that previous ETV confers either a protective or negative effect on subsequently-placed shunts. Larger studies, in a wider ranging population, are required to establish how widely these data apply. Trial registration: NCT00652470.