| 06 Sep 81 | r01        | New England PatriotsNew England P | 28 - 29 | Indianapolis ColtsIndianapolis |
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| 13 Sep 81 | r02        | Indianapolis ColtsIndianapolis | 3 - 35 | Buffalo BillsBuffalo Bills |
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| 20 Sep 81 | r03        | Denver BroncosDenver Bronco | 28 - 10 | Indianapolis ColtsIndianapolis |
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| 27 Sep 81 | r04        | Indianapolis ColtsIndianapolis | 28 - 31 | Miami DolphinsMiami Dolphin |
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| 04 Oct 81 | r05        | Buffalo BillsBuffalo Bills | 23 - 17 | Indianapolis ColtsIndianapolis |
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| 11 Oct 81 | r06        | Indianapolis ColtsIndianapolis | 19 - 41 | Cincinnati BengalsCincinnati Be |
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| 18 Oct 81 | r07        | Indianapolis ColtsIndianapolis | 14 - 43 | Los Angeles ChargersLos Angeles C |
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| 25 Oct 81 | r08        | Cleveland BrownsCleveland Bro | 42 - 28 | Indianapolis ColtsIndianapolis |
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| 01 Nov 81 | r09        | Miami DolphinsMiami Dolphin | 27 - 10 | Indianapolis ColtsIndianapolis |
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| 08 Nov 81 | r10        | Indianapolis ColtsIndianapolis | 14 - 41 | New York JetsNew York Jets |
| 15 Nov 81 | r10        | Philadelphia EaglesPhiladelphia | 38 - 13 | Indianapolis ColtsIndianapolis |
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| 22 Nov 81 | r12        | Indianapolis ColtsIndianapolis | 24 - 35 | Arizona CardinalsArizona Cardi |
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| 29 Nov 81 | r13        | New York JetsNew York Jets | 25 - 0 | Indianapolis ColtsIndianapolis |
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| 06 Dec 81 | r14        | Indianapolis ColtsIndianapolis | 13 - 37 | Dallas CowboysDallas Cowboy |
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| 13 Dec 81 | r15        | Washington CommandersWashington Co | 38 - 14 | Indianapolis ColtsIndianapolis |
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| 20 Dec 81 | r16        | Indianapolis ColtsIndianapolis | 23 - 21 | New England PatriotsNew England P |