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One thing the other answers missed is that if you setQty($qty), it will apply the exact value you provide. But if a sale was made for that product a moment before your save, the original qty could have changed. So what you really want to do is tell Magento the difference you want to apply to the qty.

Fortunately, Magento 2 provides a nice mechanism for this. Take a look at Magento\CatalogInventory\Model\ResourceModel\Stock\Item:

protected function _prepareDataForTable(\Magento\Framework\DataObject $object, $table)
{
    $data = parent::_prepareDataForTable($object, $table);
    $ifNullSql = $this->getConnection()->getIfNullSql('qty');
    if (!$object->isObjectNew() && $object->getQtyCorrection()) {
        if ($object->getQty() === null) {
            $data['qty'] = null;
        } elseif ($object->getQtyCorrection() < 0) {
            $data['qty'] = new \Zend_Db_Expr($ifNullSql . '-' . abs($object->getQtyCorrection()));
        } else {
            $data['qty'] = new \Zend_Db_Expr($ifNullSql . '+' . $object->getQtyCorrection());
        }
    }
    return $data;
}

Here we see that if you set the qty_correction value, it will apply the difference incrementally instead of applying an exact amount.

So my suggestion for a safer qty save is this:

/**
 * @var \Magento\CatalogInventory\Api\StockRegistryInterface
 */
protected $stockRegistry;

public function __construct(StockRegistryInterface $stockRegistry)
{
    $this->stockRegistry = $stockRegistry;
}

public function applyNewQty($sku, $newQty)
{
    $stockItem = $this->stockRegistry->getStockItemBySku($sku);
    $origQty = $stockItem->getQty();
    $difference = $newQty - $origQty;
    $stockItem->setQtyCorrection(difference);
    $this->stockRegistry->updateStockItemBySku($sku, $stockItem);

    // note that at this point, $stockItem->getQty() is incorrect, so you'll need to reload if you need that value
}