Clinical trials with surprising outcomes
Medicine is an evolving field as new knowledge is acquired through discoveries in the laboratory and through clinical trials.  With the acceptance of evidence-based medicine, some practices that were thought to be standard of care or represent best clinical practice have fallen out of favor as data from  randomized clinical trials emerged.
The following represents some important negative clinical studies:

# Cardiac Arrhythmia Suppression Trial
Flecainide and encainide are antiarrhythmic drugs used to prevent and treat arrhythmias (irregularities in the heart beat).  Initially, it was felt that suppressing ventricular arrhythmias after a myocardial infarction would reduce the incidence of sudden death.  However, a randomized clinical trial called the Cardiac Arrhythmia Suppression Trial (CAST) compared flecainide or encainide to placebo and found that these drugs increased mortality.  As a result, medications of this specific drug class are no longer routinely given to suppress ventricular ectopy after myocardial infarction.  (However, a different class of drugs which do have anti-arrhythmic properties, beta blockers, are routinely prescribed after a myocardial infarction.)

# Inotropic agents for congestive heart failure
Multiple inotropic agents (drugs that stimulate heart contraction) have been studied in congestive heart failure in an effort to improve symptoms and survival.  Physiologically, it would have been anticipated that drugs that enhance heart contraction would improve outcome.   However, with the notable exception of digoxin, many of these agents have had disappointing results in clinical trials, and in some cases have actually increased mortality.
One inotropic agent in particular is vesnarinone.  Initially, a short term study showed promising results.  However, when enrolled in a long term, randomized clinical trial, vesnarinone was associated with a dose-dependent increase in mortality.  This was attributed to an increase in deaths from arrhythmias.

# Liberal v. restrictive red blood cell transfusions
Initially, it was felt that hematocrits closer to the physiologic range were better than lower, more anemic hematocrits, along the lines of "more is better."  However, the Transfusion Requirements in Critical Care (TRICC) trial demonstrated that a "restrictive" transfusion policy was at least as effective as a "liberal" transfusion policy in the critical care setting.  In this trial, a restrictive transfusion strategy gave red blood cell transfusion when the hemoglobin concentration dropped below 7.0 g/dL.  The liberal strategy mandated transfusions when the hemoglobin fell below 10 g/dL.   In fact, in subset analysis, patients younger than 55-years-old had improved outcomes with a restrictive strategy.

# Bone marrow transplant for breast cancer
Given the partial success of chemotherapy to treat breast cancer, it was felt that increasing the doses of chemotherapy would lead to better outcomes.  This led to the application of high dose chemotherapy followed by rescue with the patient's own stem cells, or  autologous bone marrow transplant.  However, later studies found that autologous bone marrow transplant did not improve overall survival.

# Hormone replacement therapy
Epidemiologic studies showed that women who take hormone replacement therapy (HRT) had reduced rates of developing coronary artery disease.  However, a landmark randomized clinical trial, the Women's Health Initiative, demonstrated that hormone replacement therapy did not reduce the rates of coronary artery disease, and furthermore increased the risk of stroke.  As a result, HRT is no longer routinely recommended for prevention of coronary artery disease.