Researchers and institutional review boards often consider it inappropriate for patients to be asked to consent to more than one study despite there being no regulatory prohibition on co-enrollment in most countries. There are however ethical, safety, statistical, and practical considerations relevant to co-enrollment, particularly in surgery and perioperative medicine, but co-enrollment can be done if such concerns can be resolved. Preventing eligible patients from co-enrolling in studies which they would authentically value participating in, and whose material risks and benefits they understand, violates their autonomy - and thus contravenes a fundamental principle of research ethics. Statistical issues must be considered but can be addressed. In most cases each trial can be analyzed separately and validly using standard intention to treat principles; selection and other biases can be avoided if enrollment into the second trial is not dependent upon randomized treatment in the first trial; and valid interaction analyses can be performed for each trial by considering the patient’s status in the other trial at the time of randomization in the index trial. Clinical research with a potential to inform and improve clinical practice is valuable and should be supported. The ethical, safety, statistical, and practical aspects of co-enrollment can be managed, providing greater opportunity for research-led improvements in clinical practice.