He was 86 and had been in failing health since he fell and broke a hip in February.
Alpher's calculations supporting the Big Bang and showing how to prove its existence attracted a small flurry of interest, but fell by the wayside in a community that was committed to steady-state.
When experimental proof finally came two decades later, his contributions were overlooked in favor of those from theoreticians who had, in essence, simply repeated his work.
"It's kind of sad and, I think, unfair," physics Nobel laureate Arno Penzias said in a 1999 interview. "This poor guy has been eating himself up for 50 years. You do something great and don't get credit for it -- that shouldn't happen in a fair world. Most of the stuff we now know about the universe stems from their calculations."
It was only many years later that Alpher's contributions began to be acknowledged. In the highly regarded 1993 book, "The First Three Minutes," physics Nobel laureate Steven Weinberg described Alpher's work as "the first thoroughly modern analysis of the early history of the universe."
That recognition peaked last month, when Alpher was awarded a National Medal of Science by President Bush in a ceremony honoring recipients for 2005 and 2006. The award was accepted by Alpher's son Victor because Alpher was too ill to travel for the ceremony.
"This is yet more recognition after the miscarriage of scientific justice," said mechanical engineer Philip G. Kosky, a colleague of Alpher at General Electric and Union College. "His work is the window on the cosmos and to not win the Nobel is truly one of the great black marks on the Nobel committee."
In 1946, Alpher had just finished the research for his original doctoral thesis at George Washington University in Washington, D.C., when his mentor George Gamow showed him an article in a Russian physics journal reporting the same results.
Forced to start over, Alpher accepted a suggestion from Gamow that he study the formation of elements in the early universe, a concept known as primordial synthesis. His goal was to predict the concentrations of various elements in the universe if the Big Bang had occurred.
His calculations showed that immediately after the initial explosion, the universe was filled with radiation and other primitive matter that Alpher dubbed "ylem," a term meaning roughly "what was there before everything."
The ylem decayed to produce protons, electrons, neutrons and other particles, which eventually combined to produce the elements. Alpher calculated that it would form 10 atoms of hydrogen for every one atom of helium, precisely the ratio observed by astronomers.
Other researchers later successfully predicted the concentrations of other elements.
When it came time to publish Alpher's thesis results in the journal Physical Review, Gamow -- a former colonel in the Red army with a puckish sense of humor -- proposed adding the name of eminent physicist Hans Bethe as a coauthor. The authors thus became Alpher, Bethe and Gamow, a play on the first letters of the Greek alphabet and a popular name for a theory that dealt with the beginning of the universe.
Unfortunately, with two such distinguished physicists listed as coauthors, other scientists incorrectly assumed that Alpher had made only a small contribution to the research.
Nonetheless, the paper was published shortly before Alpher was scheduled to defend his thesis and an unprecedented 300 people -- as well as several newspaper reporters -- showed up for the defense.
Asked how long the primordial nucleosynthesis would have taken, Alpher replied 300 seconds, and a story in the next day's Washington Post was headlined: "World Began in 5 Minutes, New Theory."
Alpher quickly followed up with a second paper, written with Robert Herman of the Johns Hopkins University Applied Physics Laboratory, predicting that the radiation from the original explosion was still present in the universe, having cooled to a temperature of about 5 degrees Celsius above absolute zero, or about 450 degrees Fahrenheit below zero.