Aim: To test the feasibility of an efficacy trial comparing different flushing frequencies and volumes to reduce peripheral intravenous cannula (PIVC) failure in paediatric inpatients. Methods: Pilot, 2 × 2 factorial, randomised controlled trial comparing PIVC flushing techniques in intervention pairs: (i) low volume (3 mL) versus high volume (10 mL); and (ii) low frequency (24 hourly) versus high frequency (6 hourly). Patients were excluded if: fluids were restricted, weight < 5 kg, PIVC already in situ for >24 h or continuous infusion. The primary end-point was feasibility (eligibility, recruitment, retention, protocol adherence, missing data and sample size estimates) of a large trial. Secondary end-points were PIVC failure (composite and individual), bloodstream infection and mortality. Results: A total of 919 children were screened from April to November 2015, with 55 enrolled. Screening feasibility criteria were not met, mainly due to continuous infusions and PIVCs in situ >24 h or planned for imminent removal. However, 80% of eligible participants consented, 2% withdrew, protocol adherence was 100%, and there was no missing primary end-point data. PIVC failure was significantly higher (hazard ratio = 2.90, 95% confidence interval: 1.11–7.54) in the 3 mL compared to the 10 mL group. There was no difference in failure between frequency groups (hazard ratio = 0.91, 95% confidence interval: 0.36–2.33). There was no interaction effect (P = 0.22). Conclusion: Trial feasibility proved challenging due to eligibility criteria, which could be improved with additional recruiting staff. Firm conclusions cannot be made based on this small sample, but flush volume may impact PIVC failure.