A scientific control is an element of an experiment or observation designed to minimize the influence of variables other than the independent variable under investigation, thereby reducing the risk of confounding.

The use of controls increases the reliability and validity of results by providing a baseline for comparison between experimental measurements and control measurements. In many designs, the control group does not receive the experimental treatment, allowing researchers to isolate the effect of the independent variable.

Scientific controls are a fundamental part of the scientific method, particularly in fields such as biology, chemistry, medicine, and psychology, where complex systems are subject to multiple interacting variables.

Controls eliminate alternate explanations of experimental results, especially experimental errors and experimenter bias. Many controls are specific to the type of experiment being performed, as in the molecular markers used in SDS-PAGE experiments, and may simply have the purpose of ensuring that the equipment is working properly. The selection and use of proper controls to ensure that experimental results are valid (for example, absence of confounding variables) can be very difficult. Control measurements may also be used for other purposes: for example, a measurement of a microphone's background noise in the absence of a signal allows the noise to be subtracted from later measurements of the signal, thus producing a processed signal of higher quality.^{[citation needed]}

For example, if a researcher feeds an experimental artificial sweetener to sixty laboratories rats and observes that ten of them subsequently become sick, the underlying cause could be the sweetener itself or something unrelated. Other variables, which may not be readily obvious, may interfere with the experimental design. For instance, the artificial sweetener might be mixed with a dilutant and it might be the dilutant that causes the effect. To control for the effect of the dilutant, the same test is run twice; once with the artificial sweetener in the dilutant, and another done exactly the same way but using the dilutant alone. Now the experiment is controlled for the dilutant and the experimenter can distinguish between sweetener, dilutant, and non-treatment. Controls are most often necessary where a confounding factor cannot easily be separated from the primary treatments. For example, it may be necessary to use a tractor to spread fertilizer where there is no other practicable way to spread fertilizer. The simplest solution is to have a treatment where a tractor is driven over plots without spreading fertilizer and in that way, the effects of tractor traffic are controlled.^{[citation needed]}

The simplest types of control are negative and positive controls, and both are found in many different types of experiments. These two controls, when both are successful, are usually sufficient to eliminate most potential confounding variables: it means that the experiment produces a negative result when a negative result is expected, and a positive result when a positive result is expected. Other controls include vehicle controls, sham controls and comparative controls.

Confounding is a critical issue in observational studies because it can lead to biased or misleading conclusions about relationships between variables. A confounder is an extraneous variable that is related to both the independent variable (treatment or exposure) and the dependent variable (outcome), potentially distorting the true association. If confounding is not properly accounted for, researchers might incorrectly attribute an effect to the exposure when it is actually due to another factor. This can result in incorrect policy recommendations, ineffective interventions, or flawed scientific understanding. For example, in a study examining the relationship between physical activity and heart disease, failure to control for diet, a potential confounder, could lead to an overestimation or underestimation of the true effect of exercise.

Falsification tests are a robustness-checking technique used in observational studies to assess whether observed associations are likely due to confounding, bias, or model misspecification rather than a true causal effect. These tests help validate findings by applying the same analytical approach to a scenario where no effect is expected. If an association still appears where none should exist, it raises concerns that the primary analysis may suffer from confounding or other biases.^{[citation needed]}