Background: Although many studies have investigated sexual communication between parents and children in Kenya, none have focused singularly on grandparent and grandchild communication when grandparents are primary caregivers. Further, few studies have asked about specific topics related to sex, instead asking generally about “sex related topics” or focusing on HIV/AIDS. This research aims to investigate communication on ten specific sex- related topics between grandparents who are primary caregivers and their grandchildren. The primary research aim was to identify facilitators and barriers to grandparent-grandchild communication associated with frequency of communication. A secondary exploratory question was whether frequency of communication and youth satisfaction with communication were associated with youth’s desire for more communication in the future. Methods: The study was conducted in urban and periurban central Kenya. A convenience sample of 193 grandparents and 166 twelve to fifteen year old grandchildren were identified by community health workers. A cross sectional survey assessed nine potential barriers or facilitators to communication (e.g., frequency of communication, perceived grandparent knowledge, grandparent sense of responsibility to communication on a given topic) on ten specified sex- related topics (e.g., peer pressure on sex topics, romantic relationships, condoms). Bivariate and multivariable analyses identified significant associations between communication variables and the outcomes of interest. Results: Bivariate regression showed that higher grandchild age, grandchild gender, higher perceived grandparent knowledge, higher perceived grandparent comfort, higher grandparent-reported sense of responsibility, higher grandparent-reported belief that child should be aware of a given topic before initiating in sex, and higher youth’s own comfort during communication, were significantly associated with higher levels of communication frequency. In the multivariable model, higher grandchild age, gender, higher comfort during communication, and higher perceived grandparent knowledge remained significantly associated with higher levels communication frequency. For the secondary research question, higher communication frequency and higher levels of youth satisfaction were both significantly associated with higher levels of youth desire for more communication in bivariate regression, and higher levels of youth’s satisfaction with communication remained significantly associated with higher levels of youth’s desire for more in the adjusted analysis. Conclusions: This study found that several potential barriers and facilitators of communication are associated with both frequency of and youth’s desire for more communication. The association between grandchild age, gender and perceived grandparent knowledge and frequency of communication is similar to findings from other studies that have examined sex-related communication between parent primary caregivers and children. This finding has important implications for understanding grandparent and grandchild communication, and communication on specific topics in a population from Kenya. The positive association between youth satisfaction of and desire for more communication has important education policy and intervention implications, suggesting that if youth are satisfied with the communication with their caregivers, they may want to learn more.