Objectives To investigate differences between target and actual sample sizes, and what study characteristics were associated with sample sizes. Design Observational study. Setting The large trial registries of clinicaltrials.gov (starting in 1999) and ANZCTR (starting in 2005) through to 2021. Participants Over 280 000 interventional studies excluding studies that were withheld, terminated for safety reasons or were expanded access. Main outcome measures The actual and target sample sizes, and the within-study ratio of the actual to target sample size. Results Most studies were small: the median actual sample sizes in the two databases were 60 and 52. There was a decrease over time in the target sample size of 9%-10% per 5 years, and a larger decrease of 18%-21% per 5 years for the actual sample size. The actual-to-target sample size ratio was 4.1% lower per 5 years, meaning more studies (on average) failed to hit their target sample size. Conclusion Registered studies are more often under-recruited than over-recruited and worryingly both target and actual sample sizes appear to have decreased over time, as has the within-study gap between the target and actual sample size. Declining sample sizes and ongoing concerns about underpowered studies mean more research is needed into barriers and facilitators for improving recruitment and accessing data.