Blood is made up of red and white blood cells, and plasma. A decrease in the number or size of red cells also decreases the amount of space they occupy, resulting in a lower hematocrit. An increase in the number or size of red cells increases the amount of space they occupy, resulting in a higher hematocrit. Thalassemia is a condition which can cause an increased number of red blood cells but a decreased size and hematocrit.

The hematocrit is usually done on a person with symptoms of anemia. An anemic person has fewer or smaller than normal red cells. A low hematocrit, combined with other abnormal blood tests, confirms the diagnosis.

Some conditions, such as polycythemia, cause an overproduction of red blood cells, resulting in an increased hematocrit.

Transfusion decisions are based on the results of laboratory tests, including hematocrit. Transfusion is not considered if the hematocrit level is reasonable. The level differs for each person, depending on his or her clinical condition.

Blood drawn from a fingerstick is often used for hematocrit testing. The blood fills a small tube, which is then spun in a small centrifuge. As the tube spins, the red blood cells go to the bottom of the tube, the white blood cells cover the red in a thin layer called the buffy coat, and the liquid plasma rises to the top. The spun tube is examined for the line that divides the red cells from the buffy coat and plasma. The height of the red cell column is measured as a percent of the total blood column. The higher the column of red cells, the higher the hematocrit.

The hematocrit test can also be done on an automated instrument as part of a complete blood count. It is also called Packed Red Cell Volume or Packed Cell Volume, or abbreviated as Hct or Crit. The test is covered by insurance when medically necessary. Results are usually available the same or following day.

To collect the blood by fingerstick, a healthcare worker punctures a finger with a lancet and allows the blood to fill a small tube held to the puncture site.

Tests done on an automated instrument require 5–7 mL of blood. A healthcare worker ties a tourniquet on the person's upper arm, locates a vein in the inner elbow region, and inserts a needle into that vein. Vacuum action draws the blood through the needle into an attached tube. Collection of the sample takes only a few minutes.

Discomfort or bruising may occur at the puncture site or the person may feel dizzy or faint. Pressure to the puncture site until the bleeding stops reduces bruising. Warm packs to the puncture site relieve discomfort.

Normal values vary with age and sex. Adult male range is 42–52%, adult female 36–48%.

Hematocrit values decrease when the size or number of red cells decrease. This is most common in anemia, but other conditions have similar effects: excessive bleeding, damaged cells due to a mechanical heart valve, liver disease, and cancers affecting the bone marrow. Additional tests, and the person's symptoms and medical history help distinguish these conditions or diagnose a specific type of anemia. Hematocrit values increase when the size or number of red cells increase, such as in polycythemia.

Fluid volume in the blood affects the hematocrit. Pregnant women have extra fluid, which dilutes the blood, decreasing the hematocrit. Dehydration concentrates the blood, increasing the hematocrit.