7 Facts About Acetaminophen and Your Heart. Calf pain can be due to deep vein thrombosis (a blood clot in the leg), which is a serious and life-threatening condition. The blood clot can break loose and cause a pulmonary embolism in the lung, a heart attack, or a stroke. If you, or someone you are with, are experiencing calf or leg pain after mild exercise or exertion, or if you are experiencing pain, swelling, redness, and warmth in the calf, seek immediate medical care (call 911).