Objective: In this trial, we have observed efficacy of two different probiotics in Rotavirus and non-Rotavirus diarrhea in infants of 6 months to 12 months. Method: The study was done to observe efficacy of two different probiotic strains in Rotavirus and non- Rotavirus diarrhea in infants. The study included the infants suffering from acute severe diarrhea. 105 infants were selected and they were divided randomly into three groups. There were 35 infants in one group. The samples of stool were sent to microbiology lab for Rotavirus testing. The treatment plan was standard treatment of diarrhea for infants in group A. The treatment plan for infants of group B and group C included same standard management of diarrhea, in addition they also received probiotics Enterococcus faecium SF68 and Saccharomyces boulardii respectively. Results: There was reduction in stool output and improvement in consistency of stool in infants of group B and C as compared to infants of group A. There was decrease in stool frequency in non-Rotavirus diarrhea in infants of group B and C while there was no significant difference between groups regarding Rotavirus diarrhea. Conclusion: Probiotics helped to decrease the stool output in non-Rotavirus diarrhea. There was not any significant difference in groups regarding Rotavirus diarrhea. How to cite: Khan FA, Irum z, Khan MZ, Yousaf N, Piracha MI, Zaheer S. Effect of Probiotics on Rotavirus and Non- Rotavirus Diarrhea in Infants: Randomized Controlled Trial. Esculapio - JSIMS 2022;18(03):248-252 Keywords: Rotavirus, Non-Rotavirus, Saccharomyces boulardii,, Enterococcus faecium Sf68