Background: Praziquantel (PZQ) is currently the only recommended drug for infection and disease caused by the schistosome species that infects humans; however, the current tablet formulation is not suitable for pre-school age children mainly due to its bitterness and the large tablet size. We assessed the palatability of two new orally disintegrating tablet (ODT) formulations of PZQ. Methodology: This randomized, single-blind, crossover, swill-and-spit palatability study (NCT02315352) was carried out at a single school in Tanzania in children aged 6–11 years old, with or without schistosomiasis infection as this was not part of the assessment. Children were stratified according to age group (6–8 years or 9–11 years) and gender, then randomized to receive each formulation in a pre-specified sequence. Over 2 days, the children assessed the palatability of Levo-Praziquantel (L-PZQ) ODT 150 mg and Racemate Praziquantel (Rac-PZQ) ODT 150 mg disintegrated in the mouth without water on the first day, and L-PZQ and Rac-PZQ dispersed in water and the currently available PZQ 600 mg formulation (PZQ-Cesol) crushed and dispersed in water on the second day. The palatability of each formulation was rated using a 100 mm visual analogue scale (VAS) incorporating a 5-point hedonic scale, immediately after spitting out the test product (VASt = 0 primary outcome) and after 2–5 minutes (VASt = 2–5). Principal findings: In total, 48 children took part in the assessment. Overall, there was no reported difference in the VASt = 0 between the two ODT formulations (p = 0.106) without water. Higher VASt = 0 and VASt = 2–5 scores were reported for L-PZQ ODT compared with Rac-PZQ ODT in older children (p = 0.046 and p = 0.026, respectively). The VASt = 0 and VASt = 2–5 were higher for both ODT formulations compared with the standard formulation (p<0.001 for both time points). No serious adverse events were reported. Conclusions/Significance: The new paediatric-friendly formulations dispersed in water were both found to be more palatable than the existing standard formulation of PZQ. There may be gender and age effects on the assessment of palatability. Further research is needed for assessing efficacy and tolerability of the newly ODTs Praziquantel drug in younger children. Trial registration: The trial was registered on ClinicalTrials.gov (NCT02315352) and in the Pan African Clinical Trials Registry (PACTR201412000959159). Author summary: Schistosomiasis or Bilharzia is among the top debilitating parasitic diseases in endemic developing countries. It presents either in urinary or intestinal form. The diseases' mode of transmission is waterborne through contact with infested water. The main groups affected in developing countries are women and children due to their frequent contact with water. WHO introduced a mass drug administration program whereby drugs are distributed in endemic communities to cut off the transmission of NTDs including schistosomiasis.Praziquantel is the sole drug for the treatment of all forms of Schistosomiasis currently and it has been proven to be highly efficacious. The WHO's Preventative chemotherapy program uses the same drug as a prophylactic tool to control the disease.This drug presents a challenge in administering it to younger school children due to its size and the unpleasant taste of the available 600mg tablet. This makes it difficult to administer the correct dosage of the drug to school children and it excludes preschoolers from administration program.This study was done as a swillandspit exercise (the drug was not ingested) to assess the new orally disintegrating isomers of Praziquantel, L-PZQ and Rac-PZQ which have been prepared as 150mg tablets and sweetened through the addition of a sweetener (Sucralose), in comparision to the existing Praziquantel formulation. Findings from 48 African children showed that both new formulations are more palatable to younger children as compared to the existing Praziquantel formulation.These results provided confidence for further evaluation of the clinical efficacy and tolerability of the paediatric friendly formulations of Praziquantel tablets for schistosomiasis treatment. [ABSTRACT FROM AUTHOR]