Many factors are reported to influence blood glucose monitoring using glucometers. The common influencers include strip factors, patient factors, physical components, and pharmacological components.

Damaged or outdated test strips, deviations from ideal storage conditions (storing strips at high temperature or high humidity or with an open vial) of strips, selection of non compatible strips for glucometer can affect the reading.

The most common physical factors that affect glucometer readings are extreme temperatures and altitude. Alcohol, dirt or other substances on the skin can also influence readings. Glucose oxidase biosensor strips are often sensitive to oxygen concentration. The mediator and oxygen can both compete to take electrons from the reduced form of the glucose oxidase enzyme. Since the electrode will only pick up mediator, if the oxygen content of the sample is high, the active mediator will be lower and the value underestimated. Similarly, if the oxygen is low, the meter may report a value higher than the true value.

• Patient skill: The ability of patients to use their meter properly can influence the accuracy of a blood glucose meter.
• Monitoring issues: The reading of a glucometer can be affected if the test strip is not correctly inserted into the monitor. Replacement of the monitor batteries if not properly done also influences the monitoring and consequently the readings.
• Improper coding: Coding determines the relationship between the electrical signal produced by the strip and the reported blood glucose. Most blood glucose meters need to be coded, although some of the new meters avoid coding. Users have to make sure the code number in the device matches the code number on the test strip container.
• Hematocrit variation: Variation in hematocrit can cause serious errors in blood glucose when measured by SMBG.
• Red blood cell count: If a patient lacks sufficient red blood cells or is anemic can interfere monitoring.
• Testing site location: Blood samples from alternate sites will not be as accurate as fingertip samples when blood sugar level is rising or falling quickly. If the user feels that the reading from an alternate site is incorrect, should retry with fingertip monitoring.

Some medications such as acetaminophen, L-dopa, tolazamide, and ascorbic acid etc can alter the readings from SMBG as with electrochemical glucose oxidase systems, all seem to interact with the electrode.